[English] 日本語
Yorodumi
- PDB-5t92: ESTROGEN RECEPTOR ALPHA LIGAND BINDING DOMAIN IN COMPLEX WITH (2E... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5t92
TitleESTROGEN RECEPTOR ALPHA LIGAND BINDING DOMAIN IN COMPLEX WITH (2E)-3-{4-[(1R)-2-(4-fluorophenyl)-6-hydroxy-1-methy l-1,2,3,4- tetrahydroisoquinolin-1-yl]phenyl}prop-2-enoic acid
ComponentsEstrogen receptor
KeywordsHORMONE RECEPTOR / NUCLEAR RECEPTOR / PROTEIN-LIGAND 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-77W / Estrogen receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.22 Å
AuthorsKirby, C. / Baird, J.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ER alpha + Breast Cancer.
Authors: Burks, H.E. / Abrams, T. / Kirby, C.A. / Baird, J. / Fekete, A. / Hamann, L.G. / Kim, S. / Lombardo, F. / Loo, A. / Lubicka, D. / Macchi, K. / McDonnell, D.P. / Mishina, Y. / Norris, J.D. / ...Authors: Burks, H.E. / Abrams, T. / Kirby, C.A. / Baird, J. / Fekete, A. / Hamann, L.G. / Kim, S. / Lombardo, F. / Loo, A. / Lubicka, D. / Macchi, K. / McDonnell, D.P. / Mishina, Y. / Norris, J.D. / Nunez, J. / Saran, C. / Sun, Y. / Thomsen, N.M. / Wang, C. / Wang, J. / Peukert, S.
History
DepositionSep 9, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 29, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 26, 2017Group: Database references
Revision 1.2Mar 6, 2024Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _diffrn_radiation_wavelength.wavelength
Revision 1.3Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
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)58,6034
Polymers57,7962
Non-polymers8072
Water1,06359
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2430 Å2
ΔGint-6 kcal/mol
Surface area16750 Å2
MethodPISA
Unit cell
Length a, b, c (Å)105.220, 53.890, 97.110
Angle α, β, γ (deg.)90.000, 114.110, 90.000
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: 28897.877 Da / Num. of mol.: 2 / Fragment: residues 301-553
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-77W / (2E)-3-{4-[(1R)-2-(4-fluorophenyl)-6-hydroxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl]phenyl}prop-2-enoic acid


Mass: 403.445 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C25H22FNO3
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 59 / 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: 2.17 Å3/Da / Density % sol: 43.42 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 0.2 M Magnesium Chloride hexahydrate, 0.1 M Tris-HCl pH 8.5, 21% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 2, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.22→52.06 Å / Num. obs: 24566 / % possible obs: 98.4 % / Redundancy: 6.1 % / Biso Wilson estimate: 43.8 Å2 / Rmerge(I) obs: 0.069 / Net I/σ(I): 15.2
Reflection shellResolution: 2.22→2.34 Å / Redundancy: 5.8 % / Rmerge(I) obs: 0.446 / Mean I/σ(I) obs: 3.5 / % possible all: 94.1

-
Processing

Software
NameVersionClassification
SCALAdata scaling
BUSTER-TNT2.11.2refinement
PDB_EXTRACT3.2data extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: INTERNAL

Resolution: 2.22→52.06 Å / Cor.coef. Fo:Fc: 0.8907 / Cor.coef. Fo:Fc free: 0.8676 / SU R Cruickshank DPI: 0.265 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.257 / SU Rfree Blow DPI: 0.216 / SU Rfree Cruickshank DPI: 0.221
RfactorNum. reflection% reflectionSelection details
Rfree0.2817 1245 5.1 %RANDOM
Rwork0.2398 ---
obs0.242 24405 98.4 %-
Displacement parametersBiso max: 112.97 Å2 / Biso mean: 50.23 Å2 / Biso min: 17.8 Å2
Baniso -1Baniso -2Baniso -3
1-16.8595 Å20 Å25.3427 Å2
2---10.9541 Å20 Å2
3----5.9055 Å2
Refine analyzeLuzzati coordinate error obs: 0.356 Å
Refinement stepCycle: final / Resolution: 2.22→52.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2920 0 60 59 3039
Biso mean--39.81 45.74 -
Num. residues----366
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeight
X-RAY DIFFRACTIONt_dihedral_angle_d1078SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes65HARMONIC2
X-RAY DIFFRACTIONt_gen_planes428HARMONIC5
X-RAY DIFFRACTIONt_it3035HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion387SEMIHARMONIC5
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_contact3577SEMIHARMONIC4
LS refinement shellResolution: 2.22→2.32 Å / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.2892 162 5.75 %
Rwork0.2494 2654 -
all0.2517 2816 -
obs--98.4 %

+
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