[English] 日本語
Yorodumi
- PDB-8aus: Small molecular stabilizer for ERalpha and 14-3-3 (1080297) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8aus
TitleSmall molecular stabilizer for ERalpha and 14-3-3 (1080297)
Components
  • 14-3-3 protein sigma
  • Estrogen receptor
KeywordsSTRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / covalent
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 / regulation of epidermal cell division / protein kinase C inhibitor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis ...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 / regulation of epidermal cell division / protein kinase C inhibitor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / positive regulation of epidermal cell differentiation / epithelial cell proliferation involved in mammary gland duct elongation / keratinocyte development / epithelial cell development / keratinization / prostate epithelial cord elongation / regulation of cell-cell adhesion / mammary gland branching involved in pregnancy / negative regulation of smooth muscle cell apoptotic process / uterus development / vagina development / TFIIB-class transcription factor binding / androgen metabolic process / Regulation of localization of FOXO transcription factors / steroid hormone receptor signaling pathway / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / mammary gland alveolus development / cellular response to estrogen stimulus / establishment of skin barrier / negative regulation of protein localization to plasma membrane / estrogen response element binding / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / nuclear receptor-mediated steroid hormone signaling pathway / negative regulation of stem cell proliferation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / positive regulation of protein localization / RNA polymerase II preinitiation complex assembly / RHO GTPases activate PKNs / 14-3-3 protein binding / protein localization to chromatin / estrogen receptor signaling pathway / protein kinase A signaling / steroid binding / protein sequestering activity / nitric-oxide synthase regulator activity / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / protein export from nucleus / positive regulation of cell adhesion / ESR-mediated signaling / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / negative regulation of innate immune response / release of cytochrome c from mitochondria / negative regulation of miRNA transcription / transcription corepressor binding / positive regulation of protein export from nucleus / positive regulation of nitric-oxide synthase activity / stem cell proliferation / cellular response to estradiol stimulus / transcription coregulator binding / Translocation of SLC2A4 (GLUT4) to the plasma membrane / stem cell differentiation / nuclear estrogen receptor binding / TP53 Regulates Metabolic Genes / positive regulation of DNA-binding transcription factor activity / negative regulation of protein kinase activity / SUMOylation of intracellular receptors / euchromatin / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / Nuclear Receptor transcription pathway / beta-catenin binding / response to estrogen / Constitutive Signaling by Aberrant PI3K in Cancer / nuclear receptor activity / male gonad development / intrinsic apoptotic signaling pathway in response to DNA damage / Regulation of RUNX2 expression and activity / sequence-specific double-stranded DNA binding / positive regulation of fibroblast proliferation / positive regulation of nitric oxide biosynthetic process / protein localization / Ovarian tumor domain proteases / PIP3 activates AKT signaling / response to estradiol / regulation of protein localization / ATPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / fibroblast proliferation / positive regulation of cell growth
Similarity search - Function
Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / 14-3-3 protein sigma / Estrogen receptor/oestrogen-related receptor / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site / 14-3-3 proteins signature 1. ...Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / 14-3-3 protein sigma / Estrogen receptor/oestrogen-related receptor / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site / 14-3-3 proteins signature 1. / 14-3-3 protein / 14-3-3 homologues / 14-3-3 domain / 14-3-3 domain superfamily / 14-3-3 protein / : / 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
Similarity search - Domain/homology
Chem-O3F / Estrogen receptor / 14-3-3 protein sigma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å
AuthorsVisser, E.J. / Vandenboorn, E.M.F. / Ottmann, C.
Funding support Netherlands, 1items
OrganizationGrant numberCountry
Netherlands Organisation for Scientific Research (NWO) Netherlands
CitationJournal: J.Am.Chem.Soc. / Year: 2023
Title: Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3 sigma /ER alpha Protein-Protein Interaction from Nonselective Fragments.
Authors: Konstantinidou, M. / Visser, E.J. / Vandenboorn, E. / Chen, S. / Jaishankar, P. / Overmans, M. / Dutta, S. / Neitz, R.J. / Renslo, A.R. / Ottmann, C. / Brunsveld, L. / Arkin, M.R.
History
DepositionAug 25, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 20, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 4, 2023Group: 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 1.2Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 14-3-3 protein sigma
B: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,6745
Polymers27,1572
Non-polymers5173
Water5,585310
1
A: 14-3-3 protein sigma
B: Estrogen receptor
hetero molecules

A: 14-3-3 protein sigma
B: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,34710
Polymers54,3134
Non-polymers1,0346
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Buried area4330 Å2
ΔGint-45 kcal/mol
Surface area23920 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.879, 112.428, 62.485
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein 14-3-3 protein sigma / Epithelial cell marker protein 1 / Stratifin


Mass: 26542.914 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SFN, HME1 / Production host: Escherichia coli (E. coli) / References: UniProt: P31947
#2: Protein/peptide Estrogen receptor / ER / ER-alpha / Estradiol receptor / Nuclear receptor subfamily 3 group A member 1


Mass: 613.596 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P03372
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-O3F / 2-chloranyl-~{N}-[[7-[4-[(4-chlorophenyl)amino]oxan-4-yl]carbonyl-7-azaspiro[3.5]nonan-2-yl]methyl]ethanamide


Mass: 468.417 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H31Cl2N3O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 310 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.65 Å3/Da / Density % sol: 53.54 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.095 M HEPES (pH 7.1), PEG400 (24% (v/v)), 0.19 M CaCl2 and 5% (v/v) Glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.976254 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 3, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976254 Å / Relative weight: 1
ReflectionResolution: 1.4→45.48 Å / Num. obs: 54973 / % possible obs: 96.8 % / Redundancy: 2.5 % / CC1/2: 0.978 / Net I/σ(I): 8.5
Reflection shellResolution: 1.4→1.42 Å / Num. unique obs: 2686 / CC1/2: 0.978

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
DIALSdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4jC3

4jc3


Resolution: 1.4→45.48 Å / Cor.coef. Fo:Fc: 0.947 / Cor.coef. Fo:Fc free: 0.937 / SU B: 1.023 / SU ML: 0.042 / Cross valid method: THROUGHOUT / ESU R: 0.064 / ESU R Free: 0.065 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.21601 2784 5.1 %RANDOM
Rwork0.19378 ---
obs0.1949 52178 96.37 %-
Solvent computationIon probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.1 Å / Solvent model: MASK
Displacement parametersBiso mean: 13.729 Å2
Baniso -1Baniso -2Baniso -3
1--0 Å2-0 Å2-0 Å2
2--0.05 Å20 Å2
3----0.05 Å2
Refinement stepCycle: LAST / Resolution: 1.4→45.48 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1899 0 32 310 2241
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0171960
X-RAY DIFFRACTIONr_bond_other_d0.0010.0191857
X-RAY DIFFRACTIONr_angle_refined_deg1.5421.9022641
X-RAY DIFFRACTIONr_angle_other_deg1.2662.7014295
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.5765239
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.89722.642106
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.8815360
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.9871513
X-RAY DIFFRACTIONr_chiral_restr0.0940.2288
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.022194
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02420
X-RAY DIFFRACTIONr_mcbond_it0.941.189962
X-RAY DIFFRACTIONr_mcbond_other0.941.189961
X-RAY DIFFRACTIONr_mcangle_it1.4971.7811199
X-RAY DIFFRACTIONr_mcangle_other1.4961.7811200
X-RAY DIFFRACTIONr_scbond_it1.71.388998
X-RAY DIFFRACTIONr_scbond_other1.6991.388999
X-RAY DIFFRACTIONr_scangle_other2.5622.0051441
X-RAY DIFFRACTIONr_long_range_B_refined4.14815.6732450
X-RAY DIFFRACTIONr_long_range_B_other3.85314.9172357
LS refinement shellResolution: 1.4→1.436 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.254 198 -
Rwork0.225 3850 -
obs--96.66 %

+
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