[English] 日本語
Yorodumi
- PDB-8a62: Small molecule stabilizer (compound 2) for FOXO1 and 14-3-3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8a62
TitleSmall molecule stabilizer (compound 2) for FOXO1 and 14-3-3
Components
  • 14-3-3 protein sigma
  • Forkhead box protein O1
KeywordsSTRUCTURAL PROTEIN / 14-3-3 / FOXO1 / Stabilization
Function / homology
Function and homology information


cellular response to hyperoxia / regulation of transcription initiation by RNA polymerase II / AKT-mediated inactivation of FOXO1A / FOXO-mediated transcription of cell cycle genes / AKT phosphorylates targets in the nucleus / positive regulation of smooth muscle cell apoptotic process / neuronal stem cell population maintenance / regulation of neural precursor cell proliferation / response to fatty acid / Regulation of FOXO transcriptional activity by acetylation ...cellular response to hyperoxia / regulation of transcription initiation by RNA polymerase II / AKT-mediated inactivation of FOXO1A / FOXO-mediated transcription of cell cycle genes / AKT phosphorylates targets in the nucleus / positive regulation of smooth muscle cell apoptotic process / neuronal stem cell population maintenance / regulation of neural precursor cell proliferation / response to fatty acid / Regulation of FOXO transcriptional activity by acetylation / regulation of reactive oxygen species metabolic process / negative regulation of stress-activated MAPK cascade / negative regulation of cardiac muscle hypertrophy in response to stress / cellular response to cold / FOXO-mediated transcription of cell death genes / temperature homeostasis / negative regulation of fat cell differentiation / protein acetylation / regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / blood vessel development / keratinocyte development / fat cell differentiation / keratinization / Constitutive Signaling by AKT1 E17K in Cancer / intracellular glucose homeostasis / Regulation of gene expression in beta cells / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / cellular response to nitric oxide / negative regulation of keratinocyte proliferation / canonical Wnt signaling pathway / establishment of skin barrier / negative regulation of insulin secretion / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / positive regulation of autophagy / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / energy homeostasis / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of stem cell proliferation / RHO GTPases activate PKNs / positive regulation of gluconeogenesis / protein kinase A signaling / protein sequestering activity / negative regulation of innate immune response / protein export from nucleus / cellular response to starvation / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of protein export from nucleus / release of cytochrome c from mitochondria / protein phosphatase 2A binding / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / promoter-specific chromatin binding / TP53 Regulates Metabolic Genes / negative regulation of protein kinase activity / MAPK6/MAPK4 signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of canonical Wnt signaling pathway / chromatin DNA binding / beta-catenin binding / autophagy / DNA-binding transcription repressor activity, RNA polymerase II-specific / positive regulation of protein catabolic process / cellular response to insulin stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / insulin receptor signaling pathway / gene expression / cellular response to oxidative stress / positive regulation of cell growth / DNA-binding transcription activator activity, RNA polymerase II-specific / Interleukin-4 and Interleukin-13 signaling / sequence-specific DNA binding / nucleic acid binding / DNA-binding transcription factor activity, RNA polymerase II-specific / regulation of cell cycle / cadherin binding / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / DNA damage response / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / protein kinase binding / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular space / extracellular exosome
Similarity search - Function
: / FOXO protein, KIX-binding domain / KIX-binding domain of forkhead box O, CR2 / FOXO protein, transactivation domain / Transactivation domain of FOXO protein family / Fork head domain / Forkhead domain / Fork head domain profile. / FORKHEAD / Fork head domain conserved site 2 ...: / FOXO protein, KIX-binding domain / KIX-binding domain of forkhead box O, CR2 / FOXO protein, transactivation domain / Transactivation domain of FOXO protein family / Fork head domain / Forkhead domain / Fork head domain profile. / FORKHEAD / Fork head domain conserved site 2 / Fork head domain signature 2. / 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 / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily
Similarity search - Domain/homology
Chem-L7L / 14-3-3 protein sigma / Forkhead box protein O1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsKenanova, D.N. / Visser, E.J. / Virta, J. / Sijbesma, E. / Centorrino, F. / Zhong, M. / Vickery, H. / Neitz, J. / Brunsveld, L. / Ottmann, C. / Arkin, M.R.
Funding support Netherlands, 1items
OrganizationGrant numberCountry
Netherlands Organisation for Scientific Research (NWO)024.001.035 Netherlands
CitationJournal: Acs Cent.Sci. / Year: 2023
Title: A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers.
Authors: Kenanova, D.N. / Visser, E.J. / Virta, J.M. / Sijbesma, E. / Centorrino, F. / Vickery, H.R. / Zhong, M. / Neitz, R.J. / Brunsveld, L. / Ottmann, C. / Arkin, M.R.
History
DepositionJun 16, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 26, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 7, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Feb 7, 2024Group: 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: 14-3-3 protein sigma
B: Forkhead box protein O1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,4605
Polymers27,9312
Non-polymers5293
Water6,557364
1
A: 14-3-3 protein sigma
B: Forkhead box protein O1
hetero molecules

A: 14-3-3 protein sigma
B: Forkhead box protein O1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,92110
Polymers55,8634
Non-polymers1,0586
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Buried area5660 Å2
ΔGint-61 kcal/mol
Surface area23650 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.597, 111.503, 62.707
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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 Forkhead box protein O1 / Forkhead box protein O1A / Forkhead in rhabdomyosarcoma


Mass: 1388.406 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q12778
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-L7L / (3~{S})-1-[3,5-bis(chloranyl)-4-oxidanyl-phenyl]carbonyl-~{N}-[2-[2-(dimethylamino)ethyldisulfanyl]ethyl]piperidine-3-carboxamide


Mass: 480.472 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H27Cl2N3O3S2 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 364 / 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: 2.55 Å3/Da / Density % sol: 51.85 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.095 M HEPES pH 7.5, 0.19 M CaCl2, 5% glycerol, 24% PEG 400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, DESY / Beamline: P11 / Wavelength: 1.03322 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 4, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03322 Å / Relative weight: 1
ReflectionResolution: 1.6→45.41 Å / Num. obs: 512777 / % possible obs: 97.6 % / Redundancy: 13.8 % / CC1/2: 1 / Net I/σ(I): 39
Reflection shellResolution: 1.6→1.63 Å / Redundancy: 12.6 % / Num. unique obs: 1773 / CC1/2: 0.992

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
PDB_EXTRACT3.27data extraction
HKL-2000data reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4JC3

4jc3


Resolution: 1.6→45.41 Å / SU ML: 0.14 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 17.03 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1822 3636 5.11 %
Rwork0.1571 67464 -
obs0.1584 71100 97.44 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 59.7 Å2 / Biso mean: 17.2806 Å2 / Biso min: 1.58 Å2
Refinement stepCycle: final / Resolution: 1.6→45.41 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1937 0 43 364 2344
Biso mean--29.39 27.8 -
Num. residues----247
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 26

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.6-1.620.2121420.16472526266896
1.62-1.640.18631480.16162407255590
1.64-1.670.16951340.152592272697
1.67-1.690.20861270.15132569269697
1.69-1.720.20851420.15252582272497
1.72-1.750.20821700.16822594276497
1.75-1.780.19551350.16632539267497
1.78-1.810.23041320.16952649278198
1.81-1.840.20891620.172541270397
1.84-1.880.23521370.17382621275898
1.88-1.920.20541370.16132630276798
1.92-1.970.17231570.15762589274698
1.97-2.020.17491220.15422636275898
2.02-2.070.24451670.14862605277299
2.07-2.130.1791450.15522621276698
2.13-2.20.18481220.15292610273298
2.2-2.280.16421200.14122475259592
2.28-2.370.13961350.13992602273799
2.37-2.480.19171080.14872693280199
2.48-2.610.18011640.15332601276599
2.61-2.770.14761030.15792690279399
2.77-2.990.16711310.15672661279299
2.99-3.290.18221540.157826462800100
3.29-3.760.15281660.14492586275299
3.76-4.740.16521310.14512528265994
4.74-45.410.20831450.201226712816100

+
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