[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


NR1D1 (REV-ERBA) represses gene expression / 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 / regulation of cholesterol transporter activity / negative regulation of connective tissue replacement involved in inflammatory response wound healing / negative regulation of receptor signaling pathway via STAT / MECP2 regulates transcription factors / negative regulation of glycolytic process ...NR1D1 (REV-ERBA) represses gene expression / 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 / regulation of cholesterol transporter activity / negative regulation of connective tissue replacement involved in inflammatory response wound healing / negative regulation of receptor signaling pathway via STAT / MECP2 regulates transcription factors / negative regulation of glycolytic process / negative regulation of extracellular matrix assembly / negative regulation of vascular endothelial cell proliferation / negative regulation of cellular response to transforming growth factor beta stimulus / negative regulation of cardiac muscle hypertrophy in response to stress / arachidonic acid binding / nuclear thyroid hormone receptor binding / positive regulation of low-density lipoprotein receptor activity / positive regulation of adiponectin secretion / lipoprotein transport / negative regulation of sequestering of triglyceride / macrophage derived foam cell differentiation / positive regulation of vascular associated smooth muscle cell apoptotic process / DNA binding domain binding / STAT family protein binding / positive regulation of fatty acid metabolic process / response to lipid / negative regulation of SMAD protein signal transduction / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / Notch-HLH transcription pathway / negative regulation of fatty acid metabolic process / LBD domain binding / negative regulation of type II interferon-mediated signaling pathway / negative regulation of cholesterol storage / E-box binding / alpha-actinin binding / lipid homeostasis / locomotor rhythm / negative regulation of vascular associated smooth muscle cell proliferation / R-SMAD binding / monocyte differentiation / histone deacetylase complex / negative regulation of macrophage derived foam cell differentiation / cellular response to low-density lipoprotein particle stimulus / negative regulation of lipid storage / negative regulation of blood vessel endothelial cell migration / Regulation of MECP2 expression and activity / negative regulation of BMP signaling pathway / white fat cell differentiation / negative regulation of mitochondrial fission / positive regulation of cholesterol efflux / spindle assembly / positive regulation of fat cell differentiation / retinoic acid receptor signaling pathway / negative regulation of osteoblast differentiation / positive regulation of DNA binding / cell fate commitment / BMP signaling pathway / long-chain fatty acid transport / nuclear retinoid X receptor binding / Nuclear signaling by ERBB4 / negative regulation of signaling receptor activity / cell maturation / regulation of cellular response to insulin stimulus / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / epithelial cell differentiation / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / transcription repressor complex / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / negative regulation of angiogenesis / response to nutrient / fatty acid metabolic process / negative regulation of miRNA transcription / placenta development / negative regulation of MAP kinase activity / Regulation of PTEN gene transcription / transcription coregulator binding / HDACs deacetylate histones / nuclear receptor binding / negative regulation of smooth muscle cell proliferation / Downregulation of SMAD2/3:SMAD4 transcriptional activity / peptide binding / negative regulation of transforming growth factor beta receptor signaling pathway / Heme signaling / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / regulation of circadian rhythm / lipid metabolic process / PPARA activates gene expression / Cytoprotection by HMOX1 / NOTCH1 Intracellular Domain Regulates Transcription / mitotic spindle / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / regulation of blood pressure / DNA-binding transcription repressor activity, RNA polymerase II-specific / negative regulation of inflammatory response / positive regulation of miRNA transcription
Similarity search - Function
N-CoR, GPS2-interacting domain / G-protein pathway suppressor 2-interacting domain / SANT domain profile. / SANT domain / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Myb domain / Myb-like DNA-binding domain / Peroxisome proliferator-activated receptor ...N-CoR, GPS2-interacting domain / G-protein pathway suppressor 2-interacting domain / SANT domain profile. / SANT domain / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Myb 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 / Zinc finger, C4 type (two domains) / 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

-
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 / CAPS (buffer)


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


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


Mass: 18.015 Da / Num. of mol.: 218 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
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