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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8fkg
TitleCrystal structure of PPARgamma ligand-binding domain in complex with N-CoR peptide and inverse agonist SR33486
Components
  • Nuclear receptor corepressor 1
  • Peroxisome proliferator-activated receptor gamma
KeywordsTRANSCRIPTION / Nuclear receptors / TZDs / Drug design / Therapeutic targets / transcription-agonist complex
Function / homology
Function and homology information


: / Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / prostaglandin receptor activity / negative regulation of receptor signaling pathway via STAT / negative regulation of glycolytic process / 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 ...: / Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / prostaglandin receptor activity / negative regulation of receptor signaling pathway via STAT / negative regulation of glycolytic process / 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 / nuclear thyroid hormone receptor binding / positive regulation of cholesterol transport / : / negative regulation of cellular response to transforming growth factor beta stimulus / negative regulation of JNK cascade / arachidonate binding / positive regulation of adiponectin secretion / DNA binding domain binding / lipoprotein transport / negative regulation of cardiac muscle hypertrophy in response to stress / positive regulation of vascular associated smooth muscle cell apoptotic process / WW domain binding / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / positive regulation of fatty acid metabolic process / STAT family protein binding / response to lipid / negative regulation of fatty acid metabolic process / negative regulation of SMAD protein signal transduction / negative regulation of type II interferon-mediated signaling pathway / LBD domain binding / Notch-HLH transcription pathway / negative regulation of cholesterol storage / lipid homeostasis / E-box binding / locomotor rhythm / alpha-actinin binding / R-SMAD binding / negative regulation of vascular associated smooth muscle cell proliferation / negative regulation of blood vessel endothelial cell migration / monocyte differentiation / white fat cell differentiation / negative regulation of macrophage derived foam cell differentiation / histone deacetylase complex / negative regulation of lipid storage / cellular response to low-density lipoprotein particle stimulus / Regulation of MECP2 expression and activity / positive regulation of cholesterol efflux / negative regulation of BMP signaling pathway / cell fate commitment / negative regulation of mitochondrial fission / negative regulation of osteoblast differentiation / positive regulation of fat cell differentiation / BMP signaling pathway / long-chain fatty acid transport / nuclear retinoid X receptor binding / Nuclear signaling by ERBB4 / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / retinoic acid receptor signaling pathway / cell maturation / negative regulation of MAPK cascade / spindle assembly / intracellular receptor signaling pathway / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / hormone-mediated signaling pathway / positive regulation of adipose tissue development / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / epithelial cell differentiation / regulation of cellular response to insulin stimulus / transcription repressor complex / response to nutrient / peptide binding / negative regulation of miRNA transcription / placenta development / negative regulation of angiogenesis / transcription coregulator binding / positive regulation of apoptotic signaling pathway / Regulation of PTEN gene transcription / nuclear receptor binding / HDACs deacetylate histones / fatty acid metabolic process / SUMOylation of intracellular receptors / negative regulation of smooth muscle cell proliferation / negative regulation of transforming growth factor beta receptor signaling pathway / Downregulation of SMAD2/3:SMAD4 transcriptional activity / mRNA transcription by RNA polymerase II / Heme signaling / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / regulation of circadian rhythm / Cytoprotection by HMOX1 / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / NOTCH1 Intracellular Domain Regulates Transcription / regulation of blood pressure / lipid metabolic process / positive regulation of miRNA transcription / negative regulation of inflammatory response / DNA-binding transcription repressor activity, RNA polymerase II-specific / Constitutive Signaling by NOTCH1 PEST Domain Mutants
Similarity search - Function
N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / SANT domain profile. / Myb domain / SANT domain / Myb-like DNA-binding domain ...N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / SANT domain profile. / Myb domain / SANT domain / Myb-like DNA-binding domain / Peroxisome proliferator-activated receptor / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / : / Nuclear hormone receptor / Homeobox-like domain superfamily / 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
: / : / Nuclear receptor corepressor 1 / Peroxisome proliferator-activated receptor gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.12 Å
AuthorsMacTavish, B.S. / 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 21, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 17, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 20, 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
D: Nuclear receptor corepressor 1
A: Peroxisome proliferator-activated receptor gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,13415
Polymers34,0152
Non-polymers1,11913
Water2,216123
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3020 Å2
ΔGint-5 kcal/mol
Surface area14320 Å2
MethodPISA
Unit cell
Length a, b, c (Å)61.968, 61.968, 163.608
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212
Space group name HallP4abw2nw
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+1/4
#3: y+1/2,-x+1/2,z+3/4
#4: x+1/2,-y+1/2,-z+3/4
#5: -x+1/2,y+1/2,-z+1/4
#6: -x,-y,z+1/2
#7: y,x,-z
#8: -y,-x,-z+1/2
Components on special symmetry positions
IDModelComponents
11A-637-

HOH

-
Components

-
Protein/peptide / Protein , 2 types, 2 molecules DA

#1: Protein/peptide Nuclear receptor corepressor 1 / N-CoR / N-CoR1


Mass: 2508.824 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NCOR1, KIAA1047 / Production host: Escherichia coli (E. coli) / References: UniProt: O75376
#2: Protein Peroxisome proliferator-activated receptor gamma / PPAR-gamma / Nuclear receptor subfamily 1 group C member 3


Mass: 31506.574 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPARG, NR1C3 / Production host: Escherichia coli (E. coli) / References: UniProt: P37231

-
Non-polymers , 6 types, 136 molecules

#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-Y62 / 2-chloro-N-(5-cyanopyridin-2-yl)-5-nitrobenzamide


Mass: 302.673 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H7ClN4O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#6: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C2H6O2
#7: Chemical ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: K
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 123 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.21 Å3/Da / Density % sol: 44.41 %
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: Jul 21, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.12→30.98 Å / Num. obs: 18917 / % possible obs: 99.9 % / Redundancy: 25.2 % / Biso Wilson estimate: 33.87 Å2 / Rmerge(I) obs: 0.1486 / Net I/σ(I): 29.48
Reflection shellResolution: 2.12→2.195 Å / Redundancy: 26.4 % / Rmerge(I) obs: 1.084 / Mean I/σ(I) obs: 4.01 / Num. unique obs: 1851 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.20.1-4487refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.12→30.98 Å / SU ML: 0.2209 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.374
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2183 965 5.1 %
Rwork0.1852 17949 -
obs0.1869 18916 99.9 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 45.16 Å2
Refinement stepCycle: LAST / Resolution: 2.12→30.98 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2214 0 70 123 2407
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00282307
X-RAY DIFFRACTIONf_angle_d0.46673087
X-RAY DIFFRACTIONf_chiral_restr0.0357353
X-RAY DIFFRACTIONf_plane_restr0.0038388
X-RAY DIFFRACTIONf_dihedral_angle_d11.1832889
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.12-2.230.28681560.22422497X-RAY DIFFRACTION99.96
2.23-2.370.24361380.20062486X-RAY DIFFRACTION100
2.37-2.550.25561320.20462512X-RAY DIFFRACTION99.96
2.55-2.810.23481290.18782549X-RAY DIFFRACTION100
2.81-3.220.22031410.19592538X-RAY DIFFRACTION99.96
3.22-4.050.20611330.16732598X-RAY DIFFRACTION99.96
4.05-30.980.19261360.17922769X-RAY DIFFRACTION99.86
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)
17.08233845725-1.436547392150.3762469454053.83692419364-4.500649656676.719436519180.6756692375350.318610504913-0.324250075296-0.444810555738-0.01753817787371.371886236360.218260888851-0.971629393913-0.4102768909580.2092003751730.103290287796-0.08744971183550.678755162851-0.09476003935050.741327821003-14.53318.9027.61
20.5941600074050.6746360586560.1732735801655.93367087786-2.043151641991.050312601630.103039272389-0.2063787559060.06255065930850.752663389594-0.1633904498910.058580315224-0.424862775971-0.08998921437450.1131011823550.2974786880720.0275896493467-0.004540964049820.378502838278-0.06612459739330.2267440461218.31520.18620.634
35.61331124462-1.26066519084-0.477712224512.78421807631-1.878163330853.008858903630.264364921892-0.869609960065-0.496158107790.3370832929810.1662896663650.6148219599710.231414662071-0.4257886555-0.0470940159730.32205837959-0.1198222445320.1826031327140.6995281934140.04168410716030.569986196089-7.31-4.22731.083
41.23651087381-0.4327437001060.1471726433554.45105481548-2.140960216741.896801775960.0244334494566-0.0788431110493-0.0348115346047-0.06241869686870.04153607247650.4541125063880.0162577273565-0.393728045823-0.00916413402870.158784898360.0342674924204-0.0179515117560.348534182753-0.03078654163780.275929072038-1.3228.48514.554
54.506253390770.8037253867820.6847328661253.400460169380.07623749331383.05066344190.03815025664930.515653365986-0.0871852673438-0.432633558890.0480911734627-0.0339676117667-0.152278597870.191045478053-0.07770223150270.2123100880980.06878279171680.002729779108150.23832871637-0.02994465807210.1882026285299.51320.8294.629
65.004511318715.7997335232-1.09169863849.251203976090.2092343301264.9689089324-0.3031443699410.94202842526-0.593200594942-0.2241817661810.3686540347720.2356676066240.499873491744-0.57218793578-0.05472514309110.2721712767860.0504138315805-0.02794704206260.393155162154-0.05901027269640.3531051023252.3634.1884.747
75.66920774022-2.54998205430.4183065843151.62707855317-1.578032765154.06638364301-0.09586389088790.206120900879-0.787634834339-0.3319164561890.425042749510.8597078284510.67727984269-0.9003765292640.1825204241040.355268105496-0.157427994507-0.02240224625150.5554072270410.001791739543330.49698653807-9.312-4.1219.906
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN D AND RESID 2260:2271 )D2260 - 2271
2X-RAY DIFFRACTION2( CHAIN A AND RESID 202:251 )A202 - 251
3X-RAY DIFFRACTION3( CHAIN A AND RESID 252:276 )A252 - 276
4X-RAY DIFFRACTION4( CHAIN A AND RESID 277:377 )A277 - 377
5X-RAY DIFFRACTION5( CHAIN A AND RESID 378:430 )A378 - 430
6X-RAY DIFFRACTION6( CHAIN A AND RESID 431:458 )A431 - 458
7X-RAY DIFFRACTION7( CHAIN A AND RESID 459:477 )A459 - 477

+
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