[English] 日本語
Yorodumi
- PDB-7rs8: Crystal Structure of the ER-alpha Ligand-binding Domain (L372S, L... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7rs8
TitleCrystal Structure of the ER-alpha Ligand-binding Domain (L372S, L536S) in complex with DMERI-16
Components(Estrogen receptor) x 2
KeywordsTRANSCRIPTION/TRANSCRIPTION INHIBITOR / ER-alpha / ligand complex / DMERI / TRANSCRIPTION / TRANSCRIPTION-TRANSCRIPTION INHIBITOR complex
Function / homology
Function and homology information


regulation of epithelial cell apoptotic process / antral ovarian follicle growth / 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 / nuclear estrogen receptor activity / epithelial cell development / steroid hormone receptor signaling pathway / epithelial cell proliferation involved in mammary gland duct elongation ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / 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 / nuclear estrogen receptor activity / epithelial cell development / steroid hormone receptor signaling pathway / epithelial cell proliferation involved in mammary gland duct elongation / prostate epithelial cord elongation / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / mammary gland branching involved in pregnancy / uterus development / negative regulation of smooth muscle cell apoptotic process / vagina development / TFIIB-class transcription factor binding / androgen metabolic process / mammary gland alveolus development / cellular response to estrogen stimulus / estrogen response element binding / Mitochondrial unfolded protein response (UPRmt) / nuclear receptor-mediated steroid hormone signaling pathway / positive regulation of DNA-binding transcription factor activity / negative regulation of DNA-binding transcription factor activity / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / positive regulation of nitric-oxide synthase activity / estrogen receptor signaling pathway / protein localization to chromatin / steroid binding / 14-3-3 protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / negative regulation of canonical NF-kappaB signal transduction / ESR-mediated signaling / TBP-class protein binding / negative regulation of miRNA transcription / nitric-oxide synthase regulator activity / nuclear estrogen receptor binding / transcription corepressor binding / transcription coregulator binding / stem cell differentiation / SUMOylation of intracellular receptors / cellular response to estradiol stimulus / euchromatin / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / transcription coactivator binding / male gonad development / nuclear receptor activity / positive regulation of fibroblast proliferation / Constitutive Signaling by Aberrant PI3K in Cancer / Regulation of RUNX2 expression and activity / sequence-specific double-stranded DNA binding / positive regulation of nitric oxide biosynthetic process / Ovarian tumor domain proteases / response to estradiol / PIP3 activates AKT signaling / positive regulation of cytosolic calcium ion concentration / ATPase binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / regulation of inflammatory response / DNA-binding transcription activator activity, RNA polymerase II-specific / fibroblast proliferation / phospholipase C-activating G protein-coupled receptor signaling pathway / transcription regulator complex / Estrogen-dependent gene expression / DNA-binding transcription factor activity, RNA polymerase II-specific / calmodulin binding / Extra-nuclear estrogen signaling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin remodeling / DNA-binding transcription factor activity / negative regulation of gene expression / chromatin binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / protein kinase binding / chromatin / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / Golgi apparatus / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / identical protein binding / nucleus / membrane / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Oestrogen-type nuclear receptor final C-terminal domain / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor / : / Oestrogen receptor / Estrogen receptor/oestrogen-related receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor ...Oestrogen-type nuclear receptor final C-terminal domain / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor / : / Oestrogen receptor / 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 / Double treble clef zinc finger, C4 type / 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-7EI / Estrogen receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.64 Å
AuthorsMin, J. / Nwachukwu, J.C. / Min, C.K. / Njeri, J.W. / Srinivasan, S. / Rangarajan, E.S. / Nettles, C.C. / Yan, S. / Houtman, R. / Griffin, P.R. ...Min, J. / Nwachukwu, J.C. / Min, C.K. / Njeri, J.W. / Srinivasan, S. / Rangarajan, E.S. / Nettles, C.C. / Yan, S. / Houtman, R. / Griffin, P.R. / Izard, T. / Katzenellenbogen, B.S. / Katzenellenbogen, J.A. / Nettles, K.W.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2021
Title: Dual-mechanism estrogen receptor inhibitors.
Authors: Min, J. / Nwachukwu, J.C. / Min, C.K. / Njeri, J.W. / Srinivasan, S. / Rangarajan, E.S. / Nettles, C.C. / Sanabria Guillen, V. / Ziegler, Y. / Yan, S. / Carlson, K.E. / Hou, Y. / Kim, S.H. / ...Authors: Min, J. / Nwachukwu, J.C. / Min, C.K. / Njeri, J.W. / Srinivasan, S. / Rangarajan, E.S. / Nettles, C.C. / Sanabria Guillen, V. / Ziegler, Y. / Yan, S. / Carlson, K.E. / Hou, Y. / Kim, S.H. / Novick, S. / Pascal, B.D. / Houtman, R. / Griffin, P.R. / Izard, T. / Katzenellenbogen, B.S. / Katzenellenbogen, J.A. / Nettles, K.W.
History
DepositionAug 11, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 22, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)120,1008
Polymers117,4654
Non-polymers2,6354
Water12,845713
1
A: Estrogen receptor
B: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,0784
Polymers58,7612
Non-polymers1,3172
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3040 Å2
ΔGint-13 kcal/mol
Surface area19720 Å2
MethodPISA
2
C: Estrogen receptor
D: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,0214
Polymers58,7042
Non-polymers1,3172
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3040 Å2
ΔGint-12 kcal/mol
Surface area19140 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.534, 58.616, 93.904
Angle α, β, γ (deg.)86.940, 75.260, 62.850
Int Tables number1
Space group name H-MP1

-
Components

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


Mass: 29380.520 Da / Num. of mol.: 3 / Fragment: Ligand binding domain / Mutation: L372S, L536S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ESR1, ESR, NR3A1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P03372
#2: Protein Estrogen receptor / ER / ER-alpha / Estradiol receptor / Nuclear receptor subfamily 3 group A member 1


Mass: 29323.469 Da / Num. of mol.: 1 / Fragment: ligand-binding domain / Mutation: L372S, L536S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ESR1, ESR, NR3A1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P03372
#3: Chemical
ChemComp-7EI / (1R,2S,4R)-5-(4-hydroxyphenyl)-N-(4-methoxyphenyl)-6-{4-[2-(piperidin-1-yl)ethoxy]phenyl}-N-(2,2,2-trifluoroethyl)-7-oxabicyclo[2.2.1]hept-5-ene-2-sulfonamide


Mass: 658.728 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C34H37F3N2O6S / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 713 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.15 Å3/Da / Density % sol: 42.84 %
Crystal growTemperature: 298 K / Method: evaporation
Details: 20-25% PEG 3350, 200 mM MgCl2, 0.1 M Bis-Tris/Hepes/Tris-HCl
PH range: 6.5 - 8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: RAYONIX MX300-HS / Detector: CCD / Date: Mar 22, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.64→90.573 Å / Num. obs: 83326 / % possible obs: 84.5 % / Redundancy: 7.6 % / CC1/2: 0.996 / Net I/σ(I): 11.8
Reflection shellResolution: 1.64→1.784 Å / Mean I/σ(I) obs: 1.3 / Num. unique obs: 4167 / CC1/2: 0.502

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
Aimlessdata scaling
PHASERphasing
PDB_EXTRACT3.25data extraction
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2QXS

2qxs


Resolution: 1.64→90.57 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.901 / SU B: 6.656 / SU ML: 0.108 / Cross valid method: THROUGHOUT / ESU R: 0.166 / ESU R Free: 0.151 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2496 4122 4.9 %RANDOM
Rwork0.2105 ---
obs0.2125 79216 69.03 %-
Solvent computationIon probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.1 Å / Solvent model: MASK
Displacement parametersBiso max: 92.28 Å2 / Biso mean: 29.285 Å2 / Biso min: 4.68 Å2
Baniso -1Baniso -2Baniso -3
1--0.42 Å2-0.26 Å2-0.2 Å2
2--0.15 Å2-0.07 Å2
3----0.15 Å2
Refinement stepCycle: final / Resolution: 1.64→90.57 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7216 0 226 713 8155
Biso mean--31.92 36.42 -
Num. residues----901
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.0187632
X-RAY DIFFRACTIONr_bond_other_d0.0010.027291
X-RAY DIFFRACTIONr_angle_refined_deg1.5221.95110346
X-RAY DIFFRACTIONr_angle_other_deg1.2352.93616888
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.175892
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.18424.231312
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.787151388
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.4341539
X-RAY DIFFRACTIONr_chiral_restr0.1090.21197
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.028039
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021448
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_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.64→1.68 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.412 14 -
Rwork0.355 234 -
obs--2.77 %
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)
11.15650.2515-0.03663.7865-1.11751.74080.0156-0.0302-0.10330.0169-0.02940.10490.15380.01950.01380.08330.03430.01260.028-0.01330.05568.101-2.446-23.974
22.3912-0.4737-0.25252.19910.35882.2245-0.058-0.1088-0.02650.1880.0530.131-0.094-0.16540.0050.08490.02420.01350.02180.00460.008-4.29619.878-25.454
31.1338-0.48650.25763.3752-0.97221.74640.00140.05280.0741-0.1402-0.03430.1195-0.0639-0.01320.03290.0649-0.00810.00980.0091-0.01420.0581-15.3749.241-69.778
43.15731.01730.7562.24190.34971.6838-0.09310.05350.1745-0.1320.03670.26070.0036-0.14550.05630.10840.00360.02940.0190.0090.0522-27.801-12.773-68.051
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A308 - 546
2X-RAY DIFFRACTION2B305 - 546
3X-RAY DIFFRACTION3C306 - 546
4X-RAY DIFFRACTION4D306 - 545

+
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