[English] 日本語
Yorodumi
- PDB-6pdz: Crystal structure of PPARgamma ligand binding domain in complex w... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6pdz
TitleCrystal structure of PPARgamma ligand binding domain in complex with SMRT peptide and inverse agonist T0070907
Components
  • Nuclear receptor corepressor 2
  • Peroxisome proliferator-activated receptor gamma
KeywordsTRANSCRIPTION / Nuclear receptors / TZDs / Drug design / Therapeutic targets
Function / homology
Function and homology information


Loss of MECP2 binding ability to the NCoR/SMRT complex / regulation of ketone metabolic process / nuclear glucocorticoid receptor binding / negative regulation of androgen receptor signaling pathway / Notch binding / prostaglandin receptor activity / : / negative regulation of receptor signaling pathway via STAT / MECP2 regulates transcription factors / negative regulation of vascular endothelial cell proliferation ...Loss of MECP2 binding ability to the NCoR/SMRT complex / regulation of ketone metabolic process / nuclear glucocorticoid receptor binding / negative regulation of androgen receptor signaling pathway / Notch 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 / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / 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 / Notch-HLH transcription pathway / 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 / negative regulation of blood vessel endothelial cell migration / monocyte differentiation / white fat cell differentiation / cellular response to low-density lipoprotein particle stimulus / negative regulation of macrophage derived foam cell differentiation / Regulation of MECP2 expression and activity / 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 / estrous cycle / nuclear retinoid X receptor binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / retinoic acid receptor signaling pathway / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / cell maturation / negative regulation of MAPK cascade / intracellular receptor signaling pathway / hormone-mediated signaling pathway / lactation / positive regulation of adipose tissue development / Regulation of lipid metabolism by PPARalpha / transcription repressor complex / response to nutrient / peroxisome proliferator activated receptor signaling pathway / epithelial cell differentiation / regulation of cellular response to insulin stimulus / peptide binding / SUMOylation of transcription cofactors / negative regulation of miRNA transcription / negative regulation of angiogenesis / cerebellum development / placenta development / Regulation of PTEN gene transcription / positive regulation of apoptotic signaling pathway / transcription coregulator binding / HDACs deacetylate histones / SUMOylation of intracellular receptors / negative regulation of smooth muscle cell proliferation / Downregulation of SMAD2/3:SMAD4 transcriptional activity / enzyme activator activity / negative regulation of transforming growth factor beta receptor signaling pathway / mRNA transcription by RNA polymerase II / PPARA activates gene expression / fatty acid metabolic process / Cytoprotection by HMOX1 / regulation of circadian rhythm / Nuclear Receptor transcription pathway / Transcriptional regulation of white adipocyte differentiation / NOTCH1 Intracellular Domain Regulates Transcription / positive regulation of miRNA transcription / lipid metabolic process / negative regulation of inflammatory response / DNA-binding transcription repressor activity, RNA polymerase II-specific / regulation of blood pressure / RNA polymerase II transcription regulator complex / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / histone deacetylase binding / nuclear matrix
Similarity search - Function
N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / SANT domain profile. / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / SANT domain / Myb domain / Peroxisome proliferator-activated receptor ...N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / SANT domain profile. / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / SANT domain / Myb domain / Peroxisome proliferator-activated receptor / Myb-like DNA-binding domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / : / Retinoid X Receptor / Retinoid X Receptor / 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
2-chloro-5-nitro-N-(pyridin-4-yl)benzamide / Peroxisome proliferator-activated receptor gamma / Nuclear receptor corepressor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / 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)R01DK101871 United States
CitationJournal: Nat Commun / Year: 2020
Title: A molecular switch regulating transcriptional repression and activation of PPAR gamma.
Authors: Shang, J. / Mosure, S.A. / Zheng, J. / Brust, R. / Bass, J. / Nichols, A. / Solt, L.A. / Griffin, P.R. / Kojetin, D.J.
History
DepositionJun 19, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 4, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Oct 9, 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
B: Peroxisome proliferator-activated receptor gamma
C: Nuclear receptor corepressor 2
A: Peroxisome proliferator-activated receptor gamma
D: Nuclear receptor corepressor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,6546
Polymers68,0994
Non-polymers5552
Water9,584532
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3830 Å2
ΔGint-17 kcal/mol
Surface area25560 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.756, 93.484, 114.607
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
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: Protein/peptide Nuclear receptor corepressor 2 / N-CoR2 / CTG repeat protein 26 / SMAP270 / Silencing mediator of retinoic acid and thyroid hormone ...N-CoR2 / CTG repeat protein 26 / SMAP270 / Silencing mediator of retinoic acid and thyroid hormone receptor / SMRT / T3 receptor-associating factor / TRAC / Thyroid- / retinoic-acid-receptor-associated corepressor


Mass: 2599.999 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NCOR2, CTG26 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9Y618
#3: Chemical ChemComp-EEY / 2-chloro-5-nitro-N-(pyridin-4-yl)benzamide


Mass: 277.663 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C12H8ClN3O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 532 / 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: 2.35 Å3/Da / Density % sol: 47.67 %
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 PEG8000

-
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→37.823 Å / Num. obs: 38114 / % possible obs: 99.6 % / Redundancy: 2 % / Biso Wilson estimate: 21.5 Å2 / Rmerge(I) obs: 0.031 / Net I/σ(I): 12.4
Reflection shellResolution: 2.1→2.18 Å / Redundancy: 2 % / Rmerge(I) obs: 0.236 / Mean I/σ(I) obs: 3 / Num. unique obs: 3776 / % possible all: 99.5

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
SCALAdata scaling
PHASERphasing
PDB_EXTRACT3.25data extraction
DIALSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6ONI

6oni


Resolution: 2.1→37.82 Å / SU ML: 0.23 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 23.39
RfactorNum. reflection% reflection
Rfree0.241 2000 5.25 %
Rwork0.191 36097 -
obs0.194 38097 99.6 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 82.9 Å2 / Biso mean: 26.78 Å2 / Biso min: 9.41 Å2
Refinement stepCycle: final / Resolution: 2.1→37.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4350 0 36 532 4918
Biso mean--24.61 31.74 -
Num. residues----543
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.1-2.15250.29811420.2296255399
2.1525-2.21070.28541400.222545100
2.2107-2.27580.28581410.21392543100
2.2758-2.34920.25211420.20722552100
2.3492-2.43310.28861380.2116250399
2.4331-2.53050.2761440.20022580100
2.5305-2.64570.26641410.19662556100
2.6457-2.78510.26011410.19442549100
2.7851-2.95960.24791430.19252585100
2.9596-3.1880.24411430.20322570100
3.188-3.50860.22681420.1812256899
3.5086-4.01580.19121450.16812611100
4.0158-5.05760.19391460.16082642100
5.0576-37.820.24861520.1998274099

+
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