[English] 日本語
Yorodumi
- PDB-8dkv: PPARg bound to JTP-426467 and Co-R peptide -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8dkv
TitlePPARg bound to JTP-426467 and Co-R peptide
Components
  • Nuclear receptor corepressor 1
  • Peroxisome proliferator-activated receptor gamma
KeywordsNUCLEAR PROTEIN / PPARg / inverse agonist / covalent / JTP-426467
Function / homology
Function and homology information


: / Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / negative regulation of JNK cascade / 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 ...: / Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / negative regulation of JNK cascade / 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 / : / 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 / STAT family protein binding / positive regulation of fatty acid metabolic process / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / 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 / negative regulation of vascular associated smooth muscle cell proliferation / R-SMAD binding / monocyte differentiation / negative regulation of blood vessel endothelial cell migration / white fat cell differentiation / negative regulation of macrophage derived foam cell differentiation / histone deacetylase complex / Regulation of MECP2 expression and activity / negative regulation of lipid storage / cellular response to low-density lipoprotein particle stimulus / negative regulation of BMP signaling pathway / positive regulation of cholesterol efflux / negative regulation of mitochondrial fission / cell fate commitment / negative regulation of osteoblast differentiation / positive regulation of fat cell differentiation / negative regulation of MAPK cascade / 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 / spindle assembly / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / intracellular receptor signaling pathway / positive regulation of adipose tissue development / hormone-mediated signaling pathway / Regulation of lipid metabolism by PPARalpha / transcription repressor complex / peroxisome proliferator activated receptor signaling pathway / epithelial cell differentiation / regulation of cellular response to insulin stimulus / response to nutrient / negative regulation of miRNA transcription / peptide binding / negative regulation of angiogenesis / transcription coregulator binding / positive regulation of apoptotic signaling pathway / Regulation of PTEN gene transcription / nuclear receptor binding / fatty acid metabolic process / HDACs deacetylate histones / placenta development / 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 / positive regulation of miRNA transcription / regulation of blood pressure / NOTCH1 Intracellular Domain Regulates Transcription / lipid metabolic process / DNA-binding transcription repressor activity, RNA polymerase II-specific / negative regulation of inflammatory response / 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 / : / Homeobox-like domain superfamily / 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
Chem-SKL / Nuclear receptor corepressor 1 / Peroxisome proliferator-activated receptor gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.59 Å
AuthorsLarsen, N.A.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J.Biol.Chem. / Year: 2022
Title: Biochemical and structural basis for the pharmacological inhibition of nuclear hormone receptor PPAR gamma by inverse agonists.
Authors: Irwin, S. / Karr, C. / Furman, C. / Tsai, J. / Gee, P. / Banka, D. / Wibowo, A.S. / Dementiev, A.A. / O'Shea, M. / Yang, J. / Lowe, J. / Mitchell, L. / Ruppel, S. / Fekkes, P. / Zhu, P. / ...Authors: Irwin, S. / Karr, C. / Furman, C. / Tsai, J. / Gee, P. / Banka, D. / Wibowo, A.S. / Dementiev, A.A. / O'Shea, M. / Yang, J. / Lowe, J. / Mitchell, L. / Ruppel, S. / Fekkes, P. / Zhu, P. / Korpal, M. / Larsen, N.A.
History
DepositionJul 6, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 7, 2022Provider: repository / Type: Initial release
Revision 1.1Apr 5, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _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
Revision 1.2Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Nov 20, 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: Peroxisome proliferator-activated receptor gamma
C: Nuclear receptor corepressor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,6736
Polymers32,7262
Non-polymers9474
Water3,927218
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: isothermal titration calorimetry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1350 Å2
ΔGint-19 kcal/mol
Surface area15480 Å2
MethodPISA
Unit cell
Length a, b, c (Å)83.160, 81.630, 48.010
Angle α, β, γ (deg.)90.000, 104.060, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-807-

HOH

-
Components

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

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


Mass: 31151.186 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
#2: Protein/peptide Nuclear receptor corepressor 1 / N-CoR / N-CoR1


Mass: 1574.885 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: O75376

-
Non-polymers , 4 types, 222 molecules

#3: Chemical ChemComp-SKL / 2-chloro-N-[4-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-5-nitrobenzamide


Mass: 407.807 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H14ClN3O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-CXS / 3-CYCLOHEXYL-1-PROPYLSULFONIC ACID


Mass: 221.317 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H19NO3S / Comment: pH buffer*YM
#5: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 218 / 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: 2.42 Å3/Da / Density % sol: 49.07 %
Crystal growTemperature: 296 K / Method: vapor diffusion, hanging drop
Details: 2+2 uL drops made from a 2:2:1 molar ratio of JTP-4:NCOR peptide:PPARg and well solution containing 1.8-2.2 M (NH3)2SO4, 0.2 M Li2SO4 and 100 mM CAPS pH 9.5. Protein formulated at 20 mg mL-1 ...Details: 2+2 uL drops made from a 2:2:1 molar ratio of JTP-4:NCOR peptide:PPARg and well solution containing 1.8-2.2 M (NH3)2SO4, 0.2 M Li2SO4 and 100 mM CAPS pH 9.5. Protein formulated at 20 mg mL-1 in 20 mM Tris, pH 8.0, 100 mM NaCl, and 1mM TCEP

-
Data collection

DiffractionMean temperature: 120 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.9999 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 13, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9999 Å / Relative weight: 1
ReflectionResolution: 1.59→46.57 Å / Num. obs: 38701 / % possible obs: 92.8 % / Redundancy: 2.7 % / CC1/2: 0.999 / Rmerge(I) obs: 0.037 / Rpim(I) all: 0.027 / Rrim(I) all: 0.046 / Net I/σ(I): 14.1 / Num. measured all: 106204
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.59-1.632.50.453673326490.7870.3310.5642.185.8
7.11-46.572.60.02512504790.9980.0170.0329.497.5

-
Processing

Software
NameVersionClassification
Aimless0.5.25data scaling
REFMAC5.8.0103refinement
PDB_EXTRACT3.27data extraction
HKL-2000data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2PRG

2prg


Resolution: 1.59→46.57 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.934 / SU B: 3.071 / SU ML: 0.106 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.11 / ESU R Free: 0.115 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.266 1955 5.1 %RANDOM
Rwork0.216 ---
obs0.2185 36745 92.58 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 145.77 Å2 / Biso mean: 36.763 Å2 / Biso min: 15.2 Å2
Baniso -1Baniso -2Baniso -3
1--0 Å2-0 Å20.01 Å2
2---0.01 Å20 Å2
3---0.01 Å2
Refinement stepCycle: final / Resolution: 1.59→46.57 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2219 0 61 222 2502
Biso mean--35.9 42.46 -
Num. residues----279
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0190.022323
X-RAY DIFFRACTIONr_bond_other_d0.0050.022311
X-RAY DIFFRACTIONr_angle_refined_deg2.0492.0173131
X-RAY DIFFRACTIONr_angle_other_deg1.3473.0095335
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7135278
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.64425.40898
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.70315437
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.623159
X-RAY DIFFRACTIONr_chiral_restr0.1270.2362
X-RAY DIFFRACTIONr_gen_planes_refined0.010.022523
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02488
LS refinement shellResolution: 1.59→1.631 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.357 133 -
Rwork0.315 2512 -
all-2645 -
obs--85.54 %

+
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