[English] 日本語
Yorodumi
- PDB-8b91: Crystal structure of mutant PPARG (C313A) and NCOR2 with an inver... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8b91
TitleCrystal structure of mutant PPARG (C313A) and NCOR2 with an inverse agonist (compound SI-1)
Components
  • Nuclear receptor corepressor 2
  • Peroxisome proliferator-activated receptor gamma
KeywordsTRANSCRIPTION / nuclear hormone receptor transcription factor
Function / homology
Function and homology information


Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / regulation of ketone metabolic process / nuclear glucocorticoid receptor binding / prostaglandin receptor 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 / Notch binding / negative regulation of extracellular matrix assembly ...Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / regulation of ketone metabolic process / nuclear glucocorticoid receptor binding / prostaglandin receptor 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 / Notch binding / negative regulation of extracellular matrix assembly / negative regulation of vascular endothelial cell proliferation / positive regulation of cholesterol transport / negative regulation of cardiac muscle hypertrophy in response to stress / negative regulation of cellular response to transforming growth factor beta stimulus / positive regulation of low-density lipoprotein receptor activity / arachidonate binding / positive regulation of adiponectin secretion / lipoprotein transport / negative regulation of sequestering of triglyceride / : / DNA binding domain binding / macrophage derived foam cell differentiation / positive regulation of vascular associated smooth muscle cell apoptotic process / STAT family protein binding / WW domain binding / positive regulation of fatty acid metabolic process / response to lipid / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of SMAD protein signal transduction / LBD domain binding / Notch-HLH transcription pathway / negative regulation of type II interferon-mediated signaling pathway / negative regulation of cholesterol storage / E-box binding / alpha-actinin binding / lipid homeostasis / negative regulation of vascular associated smooth muscle cell proliferation / R-SMAD binding / monocyte differentiation / negative regulation of blood vessel endothelial cell migration / negative regulation of macrophage derived foam cell differentiation / Regulation of MECP2 expression and activity / cellular response to low-density lipoprotein particle stimulus / negative regulation of lipid storage / white fat cell differentiation / negative regulation of BMP signaling pathway / positive regulation of cholesterol efflux / negative regulation of mitochondrial fission / estrous cycle / positive regulation of fat cell differentiation / negative regulation of osteoblast differentiation / cell fate commitment / negative regulation of MAPK cascade / BMP signaling pathway / retinoic acid receptor signaling pathway / long-chain fatty acid transport / nuclear retinoid X receptor binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / cell maturation / negative regulation of signaling receptor activity / 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 / lactation / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / regulation of cellular response to insulin stimulus / negative regulation of angiogenesis / cerebellum development / response to nutrient / negative regulation of miRNA transcription / SUMOylation of transcription cofactors / Regulation of PTEN gene transcription / transcription coregulator binding / fatty acid metabolic process / HDACs deacetylate histones / positive regulation of apoptotic signaling pathway / negative regulation of smooth muscle cell proliferation / Downregulation of SMAD2/3:SMAD4 transcriptional activity / negative regulation of transforming growth factor beta receptor signaling pathway / peptide binding / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / placenta development / regulation of circadian rhythm / PPARA activates gene expression / Cytoprotection by HMOX1 / lipid metabolic process / NOTCH1 Intracellular Domain Regulates Transcription / DNA-binding transcription repressor activity, RNA polymerase II-specific / positive regulation of miRNA transcription / negative regulation of inflammatory response / regulation of blood pressure / histone deacetylase binding / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
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 ...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-Q4O / Peroxisome proliferator-activated receptor gamma / Nuclear receptor corepressor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.23 Å
AuthorsFriberg, A. / Orsi, D.L. / Pook, E. / Siegel, S. / Lemke, C.T. / Stellfeld, T. / Puetter, V. / Goldstein, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Bioorg.Med.Chem. / Year: 2022
Title: Discovery and characterization of orally bioavailable 4-chloro-6-fluoroisophthalamides as covalent PPARG inverse-agonists.
Authors: Orsi, D.L. / Ferrara, S.J. / Siegel, S. / Friberg, A. / Bouche, L. / Pook, E. / Lienau, P. / Bluck, J.P. / Lemke, C.T. / Akcay, G. / Stellfeld, T. / Meyer, H. / Putter, V. / Holton, S.J. / ...Authors: Orsi, D.L. / Ferrara, S.J. / Siegel, S. / Friberg, A. / Bouche, L. / Pook, E. / Lienau, P. / Bluck, J.P. / Lemke, C.T. / Akcay, G. / Stellfeld, T. / Meyer, H. / Putter, V. / Holton, S.J. / Korr, D. / Jerchel-Furau, I. / Pantelidou, C. / Strathdee, C.A. / Meyerson, M. / Eis, K. / Goldstein, J.T.
History
DepositionOct 5, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 28, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 4, 2023Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2May 1, 2024Group: 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
B: Peroxisome proliferator-activated receptor gamma
C: Nuclear receptor corepressor 2
D: Nuclear receptor corepressor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)69,4355
Polymers68,9384
Non-polymers4971
Water3,549197
1
A: Peroxisome proliferator-activated receptor gamma
C: Nuclear receptor corepressor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,9663
Polymers34,4692
Non-polymers4971
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1260 Å2
ΔGint-11 kcal/mol
Surface area14100 Å2
MethodPISA
2
B: Peroxisome proliferator-activated receptor gamma
D: Nuclear receptor corepressor 2


Theoretical massNumber of molelcules
Total (without water)34,4692
Polymers34,4692
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1040 Å2
ΔGint-8 kcal/mol
Surface area13190 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.355, 86.134, 120.855
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: 31830.928 Da / Num. of mol.: 2 / Mutation: C313A
Source method: isolated from a genetically manipulated source
Details: Mutation inserted: C313A / Source: (gene. exp.) Homo sapiens (human) / Gene: PPARG, NR1C3 / Production host: Escherichia coli (E. coli) / 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: 2638.073 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q9Y618
#3: Chemical ChemComp-Q4O / ~{N}3-[4-[bis(fluoranyl)methoxy]-3-fluoranyl-phenyl]-4-chloranyl-6-fluoranyl-~{N}1-[(2-methoxyphenyl)methyl]benzene-1,3-dicarboxamide


Mass: 496.839 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H17ClF4N2O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 197 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.28 Å3/Da / Density % sol: 46.02 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: PEG 3350 20%, NaAc 0.2 M

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.9184 Å
DetectorType: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Feb 1, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
ReflectionResolution: 2.23→49.47 Å / Num. obs: 31319 / % possible obs: 99.6 % / Redundancy: 7.3 % / CC1/2: 0.996 / Rrim(I) all: 0.18 / Net I/σ(I): 11.2
Reflection shellResolution: 2.23→2.3 Å / Redundancy: 6.6 % / Mean I/σ(I) obs: 1.5 / Num. unique obs: 2810 / CC1/2: 0.419 / Rrim(I) all: 1.409 / % possible all: 99.3

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: internal

Resolution: 2.23→49.47 Å / Cor.coef. Fo:Fc: 0.947 / Cor.coef. Fo:Fc free: 0.935 / SU B: 6.755 / SU ML: 0.158 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.28 / ESU R Free: 0.2 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2277 1611 5.2 %RANDOM
Rwork0.2017 ---
obs0.2031 29654 99.41 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 110.65 Å2 / Biso mean: 39.786 Å2 / Biso min: 17.71 Å2
Baniso -1Baniso -2Baniso -3
1-0.22 Å20 Å20 Å2
2--0.11 Å2-0 Å2
3----0.33 Å2
Refinement stepCycle: final / Resolution: 2.23→49.47 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4181 0 34 197 4412
Biso mean--55.34 37.99 -
Num. residues----525
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0134309
X-RAY DIFFRACTIONr_bond_other_d0.0010.0164301
X-RAY DIFFRACTIONr_angle_refined_deg1.4421.6465799
X-RAY DIFFRACTIONr_angle_other_deg1.2411.5839925
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.425523
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.80923.951205
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.5115838
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.9821518
X-RAY DIFFRACTIONr_chiral_restr0.0650.2565
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.024738
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02907
LS refinement shellResolution: 2.23→2.288 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.349 117 -
Rwork0.312 2165 -
all-2282 -
obs--99.17 %

+
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