[English] 日本語
Yorodumi
- PDB-8btq: Small molecule stabilizer for 14-3-3/ChREBP (Cmd1-soaking) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8btq
TitleSmall molecule stabilizer for 14-3-3/ChREBP (Cmd1-soaking)
Components
  • 14-3-3 protein sigma
  • Carbohydrate-responsive element-binding protein
KeywordsSTRUCTURAL PROTEIN / 14-3-3 / ChREBP / stabilization
Function / homology
Function and homology information


carbohydrate response element binding / glucose mediated signaling pathway / AMPK inhibits chREBP transcriptional activation activity / PKA-mediated phosphorylation of key metabolic factors / PP2A-mediated dephosphorylation of key metabolic factors / positive regulation of transcription from RNA polymerase II promoter by glucose / ChREBP activates metabolic gene expression / positive regulation of fatty acid biosynthetic process / negative regulation of oxidative phosphorylation / triglyceride homeostasis ...carbohydrate response element binding / glucose mediated signaling pathway / AMPK inhibits chREBP transcriptional activation activity / PKA-mediated phosphorylation of key metabolic factors / PP2A-mediated dephosphorylation of key metabolic factors / positive regulation of transcription from RNA polymerase II promoter by glucose / ChREBP activates metabolic gene expression / positive regulation of fatty acid biosynthetic process / negative regulation of oxidative phosphorylation / triglyceride homeostasis / lipid biosynthetic process / DNA-binding transcription activator activity / regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / anatomical structure morphogenesis / negative regulation of keratinocyte proliferation / establishment of skin barrier / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / fatty acid homeostasis / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / energy homeostasis / negative regulation of peptidyl-serine phosphorylation / positive regulation of lipid biosynthetic process / protein kinase A signaling / negative regulation of stem cell proliferation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / protein export from nucleus / negative regulation of innate immune response / positive regulation of glycolytic process / protein sequestering activity / 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 / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / negative regulation of protein kinase activity / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / DNA-binding transcription repressor activity, RNA polymerase II-specific / intrinsic apoptotic signaling pathway in response to DNA damage / glucose homeostasis / positive regulation of cell growth / DNA-binding transcription activator activity, RNA polymerase II-specific / DNA-binding transcription factor binding / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / regulation of cell cycle / DNA-binding transcription factor activity, RNA polymerase II-specific / cadherin binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein heterodimerization activity / negative regulation of DNA-templated transcription / positive regulation of cell population proliferation / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / 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 / DNA binding / extracellular space / extracellular exosome / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Helix-loop-helix DNA-binding domain / 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 ...Helix-loop-helix DNA-binding domain / 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 / Helix-loop-helix DNA-binding domain superfamily / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile.
Similarity search - Domain/homology
Chem-OQE / 14-3-3 protein sigma / Carbohydrate-responsive element-binding protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsPennings, M.A.M. / Visser, E.J. / Ottmann, C.
Funding support Netherlands, 1items
OrganizationGrant numberCountry
Netherlands Organisation for Scientific Research (NWO) Netherlands
CitationJournal: Biorxiv / Year: 2024
Title: Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.
Authors: Katz, L.S. / Visser, E.J. / Plitzko, K.F. / Pennings, M. / Cossar, P.J. / Tse, I.L. / Kaiser, M. / Brunsveld, L. / Scott, D.K. / Ottmann, C.
History
DepositionNov 29, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 1, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 14-3-3 protein sigma
B: Carbohydrate-responsive element-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,4346
Polymers29,0262
Non-polymers4084
Water3,999222
1
A: 14-3-3 protein sigma
B: Carbohydrate-responsive element-binding protein
hetero molecules

A: 14-3-3 protein sigma
B: Carbohydrate-responsive element-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,86812
Polymers58,0524
Non-polymers8168
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555x,-y,-z1
Unit cell
Length a, b, c (Å)81.979, 111.932, 62.339
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 Carbohydrate-responsive element-binding protein / / ChREBP / Class D basic helix-loop-helix protein 14 / bHLHd14 / MLX interactor / MLX-interacting ...ChREBP / Class D basic helix-loop-helix protein 14 / bHLHd14 / MLX interactor / MLX-interacting protein-like / WS basic-helix-loop-helix leucine zipper protein / WS-bHLH / Williams-Beuren syndrome chromosomal region 14 protein


Mass: 2482.883 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q9NP71
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-OQE / [2-[2-oxidanylidene-2-(2-phenylethylamino)ethoxy]phenyl]phosphonic acid


Mass: 335.292 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H18NO5P / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 222 / 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: 2.36 Å3/Da / Density % sol: 47.79 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.095 M HEPES pH = 7.5 27% PEG400 0.19 M CaCl2 5% glycerol

-
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: 38129 / % possible obs: 99.9 % / Redundancy: 12.9 % / CC1/2: 0.999 / Net I/σ(I): 26
Reflection shellResolution: 1.6→1.63 Å / Num. unique obs: 1837 / CC1/2: 0.959

-
Processing

Software
NameVersionClassification
REFMAC8refinement
DIALSdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4JC3

4jc3


Resolution: 1.6→45.41 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.949 / SU B: 2.523 / SU ML: 0.047 / Cross valid method: THROUGHOUT / ESU R: 0.08 / ESU R Free: 0.081 / 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
Rfree0.19921 1856 4.9 %RANDOM
Rwork0.17168 ---
obs0.17305 36253 99.81 %-
Solvent computationIon probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1 Å / Solvent model: MASK
Displacement parametersBiso mean: 17.901 Å2
Baniso -1Baniso -2Baniso -3
1-0.39 Å20 Å2-0 Å2
2--0.3 Å20 Å2
3----0.69 Å2
Refinement stepCycle: LAST / Resolution: 1.6→45.41 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1998 0 26 222 2246
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0162052
X-RAY DIFFRACTIONr_bond_other_d0.0010.0161893
X-RAY DIFFRACTIONr_angle_refined_deg1.311.8222760
X-RAY DIFFRACTIONr_angle_other_deg0.5261.5654412
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5975.304263
X-RAY DIFFRACTIONr_dihedral_angle_2_deg4.07751
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.42910383
X-RAY DIFFRACTIONr_chiral_restr0.0610.2299
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.022329
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02403
X-RAY DIFFRACTIONr_mcbond_it2.9571.251997
X-RAY DIFFRACTIONr_mcbond_other2.9141.252997
X-RAY DIFFRACTIONr_mcangle_it4.1311.8571241
X-RAY DIFFRACTIONr_mcangle_other4.1291.8621242
X-RAY DIFFRACTIONr_scbond_it5.111.6641055
X-RAY DIFFRACTIONr_scbond_other5.1081.6651056
X-RAY DIFFRACTIONr_scangle_other6.7742.3281520
X-RAY DIFFRACTIONr_long_range_B_refined7.87622.7142488
X-RAY DIFFRACTIONr_long_range_B_other7.77220.7372429
LS refinement shellResolution: 1.6→1.642 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.204 112 -
Rwork0.174 2661 -
obs--99.6 %
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)
10.5922-0.22650.34120.5568-0.2470.792-0.0379-0.03040.0150.04290.0114-0.0315-0.03420.03170.02650.05470.0060.00240.0123-0.00330.0062-23.777-17.0647.678
24.3194-0.6038-0.53696.63341.2286.41410.0839-0.02640.5076-0.1544-0.1907-0.366-0.39340.20740.10680.077-0.0012-0.01890.03730.04230.1644-11.716-8.95111.376

+
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