[English] 日本語
Yorodumi
- PDB-8aze: Small molecule stabilizer for ERalpha and 14-3-3 (1075306) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8aze
TitleSmall molecule stabilizer for ERalpha and 14-3-3 (1075306)
Components
  • 14-3-3 protein sigma
  • ERalpha peptide
KeywordsSTRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilizer
Function / homology
Function and homology information


regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / regulation of cell-cell adhesion / cAMP/PKA signal transduction / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding ...regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / regulation of cell-cell adhesion / cAMP/PKA signal transduction / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / establishment of skin barrier / negative regulation of protein localization to plasma membrane / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / negative regulation of protein kinase activity / negative regulation of stem cell proliferation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / positive regulation of protein localization / positive regulation of cell adhesion / protein sequestering activity / protein export from nucleus / negative regulation of innate immune response / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / positive regulation of protein export from nucleus / stem cell proliferation / TP53 Regulates Metabolic Genes / Translocation of SLC2A4 (GLUT4) to the plasma membrane / intrinsic apoptotic signaling pathway in response to DNA damage / intracellular protein localization / regulation of protein localization / positive regulation of cell growth / regulation of cell cycle / cadherin binding / protein kinase binding / negative regulation of transcription by RNA polymerase II / signal transduction / extracellular space / extracellular exosome / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
14-3-3 protein sigma / 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
Similarity search - Domain/homology
Chem-O5I / 14-3-3 protein sigma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsKonstantinidou, M. / Visser, E.J. / Vandenboorn, E.M.F. / Sheng, C. / Jaishankar, P. / Overmans, M.J.A.M. / Dutta, S. / Neitz, J. / Renslo, A. / Ottmann, C. ...Konstantinidou, M. / Visser, E.J. / Vandenboorn, E.M.F. / Sheng, C. / Jaishankar, P. / Overmans, M.J.A.M. / Dutta, S. / Neitz, J. / Renslo, A. / Ottmann, C. / Brunsveld, L. / Arkin, M.
Funding support Netherlands, 1items
OrganizationGrant numberCountry
Netherlands Organisation for Scientific Research (NWO)024.001.035 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
DepositionSep 6, 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 1.2Nov 6, 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: ERalpha peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,6426
Polymers27,1572
Non-polymers4854
Water5,224290
1
A: 14-3-3 protein sigma
B: ERalpha peptide
hetero molecules

A: 14-3-3 protein sigma
B: ERalpha peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,28412
Polymers54,3134
Non-polymers9718
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Buried area4390 Å2
ΔGint-45 kcal/mol
Surface area23570 Å2
Unit cell
Length a, b, c (Å)81.846, 111.849, 62.305
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-302-

MG

-
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 ERalpha peptide


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


Mass: 24.305 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-O5I / 2-chloranyl-~{N}-[[1-[1-[(4-chlorophenyl)amino]cyclopentyl]carbonylpiperidin-4-yl]methyl]ethanamide


Mass: 412.353 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H27Cl2N3O2 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 290 / 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: 2.62 Å3/Da / Density % sol: 53.13 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 35% (v/v) 2-Ethoxyethanol, 100 mM Imidazole/ Hydrochloric acid pH 8.0, 50 mM Calcium acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 1.0332 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Nov 26, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 1.6→45.32 Å / Num. obs: 37965 / % possible obs: 99.71 % / Redundancy: 4.7 % / CC1/2: 0.997 / Net I/σ(I): 17.6
Reflection shellResolution: 1.6→1.657 Å / Num. unique obs: 3725 / CC1/2: 0.968

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
XDSdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4JC3

4jc3


Resolution: 1.6→45.32 Å / Cor.coef. Fo:Fc: 0.958 / Cor.coef. Fo:Fc free: 0.939 / SU B: 1.324 / SU ML: 0.048 / Cross valid method: THROUGHOUT / ESU R: 0.078 / ESU R Free: 0.081 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2013 1852 4.9 %RANDOM
Rwork0.16706 ---
obs0.16878 36144 99.63 %-
Solvent computationIon probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 17.974 Å2
Baniso -1Baniso -2Baniso -3
1-0.35 Å20 Å2-0 Å2
2---0.1 Å20 Å2
3----0.25 Å2
Refinement stepCycle: LAST / Resolution: 1.6→45.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1898 0 29 290 2217
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0171954
X-RAY DIFFRACTIONr_bond_other_d0.0010.0191853
X-RAY DIFFRACTIONr_angle_refined_deg1.331.8992630
X-RAY DIFFRACTIONr_angle_other_deg1.2472.7034285
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.8675239
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.52722.642106
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.89915360
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.9531513
X-RAY DIFFRACTIONr_chiral_restr0.0820.2287
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.022190
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02420
X-RAY DIFFRACTIONr_mcbond_it8.0731.48962
X-RAY DIFFRACTIONr_mcbond_other8.0731.479961
X-RAY DIFFRACTIONr_mcangle_it9.4152.1951199
X-RAY DIFFRACTIONr_mcangle_other9.4132.1951200
X-RAY DIFFRACTIONr_scbond_it11.2971.929992
X-RAY DIFFRACTIONr_scbond_other11.2911.929993
X-RAY DIFFRACTIONr_scangle_other11.6962.6171432
X-RAY DIFFRACTIONr_long_range_B_refined12.23218.6172438
X-RAY DIFFRACTIONr_long_range_B_other12.3117.9292356
LS refinement shellResolution: 1.6→1.641 Å
RfactorNum. reflection% reflection
Rfree0.263 110 -
Rwork0.173 2610 -
obs--97.95 %

+
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