[English] 日本語
Yorodumi
- PDB-8fhf: Crystal structure of PPARgamma ligand-binding domain in complex w... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8fhf
TitleCrystal structure of PPARgamma ligand-binding domain in complex with ZINC5672437
ComponentsPeroxisome proliferator-activated receptor gamma
KeywordsTRANSCRIPTION / Nuclear receptors / TZDs / Drug design / Therapeutic targets / transcription-agonist complex
Function / homology
Function and homology information


prostaglandin receptor activity / : / negative regulation of receptor signaling pathway via STAT / MECP2 regulates transcription factors / negative regulation of vascular endothelial cell proliferation / negative regulation of extracellular matrix assembly / negative regulation of connective tissue replacement involved in inflammatory response wound healing / positive regulation of cholesterol transport / negative regulation of cellular response to transforming growth factor beta stimulus / arachidonate binding ...prostaglandin receptor activity / : / negative regulation of receptor signaling pathway via STAT / MECP2 regulates transcription factors / negative regulation of vascular endothelial cell proliferation / negative regulation of extracellular matrix assembly / negative regulation of connective tissue replacement involved in inflammatory response wound healing / positive regulation of cholesterol transport / negative regulation of cellular response to transforming growth factor beta stimulus / arachidonate binding / positive regulation of adiponectin secretion / negative regulation of cardiac muscle hypertrophy in response to stress / DNA binding domain binding / lipoprotein transport / positive regulation of vascular associated smooth muscle cell apoptotic process / WW domain binding / positive regulation of fatty acid metabolic process / STAT family protein binding / response to lipid / negative regulation of type II interferon-mediated signaling pathway / LBD domain binding / negative regulation of cholesterol storage / negative regulation of SMAD protein signal transduction / lipid homeostasis / E-box binding / alpha-actinin binding / R-SMAD binding / negative regulation of vascular associated smooth muscle cell proliferation / monocyte differentiation / negative regulation of blood vessel endothelial cell migration / white fat cell differentiation / negative regulation of macrophage derived foam cell differentiation / cellular response to low-density lipoprotein particle stimulus / negative regulation of lipid storage / negative regulation of BMP signaling pathway / positive regulation of cholesterol efflux / cell fate commitment / negative regulation of osteoblast differentiation / negative regulation of mitochondrial fission / positive regulation of fat cell differentiation / BMP signaling pathway / long-chain fatty acid transport / nuclear retinoid X receptor binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / retinoic acid receptor signaling pathway / cell maturation / negative regulation of MAPK cascade / intracellular receptor signaling pathway / hormone-mediated signaling pathway / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / response to nutrient / epithelial cell differentiation / regulation of cellular response to insulin stimulus / peptide binding / negative regulation of miRNA transcription / negative regulation of angiogenesis / placenta development / Regulation of PTEN gene transcription / positive regulation of apoptotic signaling pathway / transcription coregulator binding / SUMOylation of intracellular receptors / negative regulation of smooth muscle cell proliferation / mRNA transcription by RNA polymerase II / negative regulation of transforming growth factor beta receptor signaling pathway / fatty acid metabolic process / PPARA activates gene expression / regulation of circadian rhythm / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / lipid metabolic process / positive regulation of miRNA transcription / regulation of blood pressure / negative regulation of inflammatory response / DNA-binding transcription repressor activity, RNA polymerase II-specific / RNA polymerase II transcription regulator complex / nuclear receptor activity / cellular response to insulin stimulus / rhythmic process / glucose homeostasis / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / double-stranded DNA binding / DNA-binding transcription activator activity, RNA polymerase II-specific / cellular response to hypoxia / DNA-binding transcription factor binding / sequence-specific DNA binding / nucleic acid binding / DNA-binding transcription factor activity, RNA polymerase II-specific / cell differentiation / receptor complex / transcription cis-regulatory region binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / innate immune response / negative regulation of DNA-templated transcription / intracellular membrane-bounded organelle / chromatin binding / positive regulation of gene expression / regulation of transcription by RNA polymerase II
Similarity search - Function
Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Peroxisome proliferator-activated receptor / : / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / Nuclear hormone receptors DNA-binding domain profile. ...Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Peroxisome proliferator-activated receptor / : / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / 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
nonanoic acid / : / Peroxisome proliferator-activated receptor gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsShang, J. / Kojetin, D.J.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)6R01DK124870 United States
CitationJournal: Nat Commun / Year: 2025
Title: Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.
Authors: MacTavish, B.S. / Zhu, D. / Shang, J. / Shao, Q. / He, Y. / Yang, Z.J. / Kamenecka, T.M. / Kojetin, D.J.
History
DepositionDec 14, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 20, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification
Revision 1.2Apr 30, 2025Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Peroxisome proliferator-activated receptor gamma
B: Peroxisome proliferator-activated receptor gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,8556
Polymers62,8992
Non-polymers9564
Water4,648258
1
A: Peroxisome proliferator-activated receptor gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9273
Polymers31,4501
Non-polymers4782
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Peroxisome proliferator-activated receptor gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9273
Polymers31,4501
Non-polymers4782
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)91.635, 60.695, 117.076
Angle α, β, γ (deg.)90.00, 102.51, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Peroxisome proliferator-activated receptor gamma / PPAR-gamma / Nuclear receptor subfamily 1 group C member 3


Mass: 31449.520 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPARG, NR1C3 / Plasmid: pET46 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P37231
#2: Chemical ChemComp-XZK / N-(4-carbamoylphenyl)-2-chloro-5-nitrobenzamide


Mass: 319.700 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H10ClN3O4
#3: Chemical ChemComp-KNA / nonanoic acid


Mass: 158.238 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H18O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 258 / 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: 2.53 Å3/Da / Density % sol: 51.32 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 0.2M Ammonium sulfate, 0.1M MES, pH 6.5, 30% w/v, PEG 8000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97946 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 26, 2019
RadiationMonochromator: Liquid nitrogen-cooled double crystal Si(111)
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.1→38.89 Å / Num. obs: 35970 / % possible obs: 97.43 % / Redundancy: 2 % / Biso Wilson estimate: 21.52 Å2 / CC1/2: 0.999 / CC star: 1 / Rmerge(I) obs: 0.01582 / Rpim(I) all: 0.01582 / Rrim(I) all: 0.02237 / Net I/σ(I): 16.87
Reflection shellResolution: 2.1→2.175 Å / Rmerge(I) obs: 0.2458 / Num. unique obs: 3565 / CC1/2: 0.961 / CC star: 0.99 / Rpim(I) all: 0.2458 / Rrim(I) all: 0.3477 / Χ2: 2.07

-
Processing

Software
NameVersionClassification
SCALAdata scaling
PHENIX1.11.1_2575refinement
PDB_EXTRACT3.25data extraction
DIALSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→38.89 Å / SU ML: 0.3 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 30.12 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.285 2000 5.57 %
Rwork0.2329 --
obs0.2358 35927 97.46 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.1→38.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4034 0 64 258 4356
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0084316
X-RAY DIFFRACTIONf_angle_d1.0085799
X-RAY DIFFRACTIONf_dihedral_angle_d7.1742653
X-RAY DIFFRACTIONf_chiral_restr0.05663
X-RAY DIFFRACTIONf_plane_restr0.006735
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1-2.15250.35821400.31922374X-RAY DIFFRACTION98
2.1525-2.21070.37951450.31092452X-RAY DIFFRACTION98
2.2107-2.27580.33641420.30112423X-RAY DIFFRACTION98
2.2758-2.34920.32361410.28972376X-RAY DIFFRACTION97
2.3492-2.43320.35831340.28422289X-RAY DIFFRACTION92
2.4332-2.53060.36481440.26932436X-RAY DIFFRACTION99
2.5306-2.64570.33861460.26752468X-RAY DIFFRACTION99
2.6457-2.78520.28991420.25172426X-RAY DIFFRACTION99
2.7852-2.95960.32111450.24672443X-RAY DIFFRACTION99
2.9596-3.1880.31450.24192474X-RAY DIFFRACTION99
3.188-3.50870.26271370.22042318X-RAY DIFFRACTION93
3.5087-4.01590.24261470.19182487X-RAY DIFFRACTION99
4.0159-5.05790.22991460.17742490X-RAY DIFFRACTION99
5.0579-38.890.22351460.18762471X-RAY DIFFRACTION96

+
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