[English] 日本語
Yorodumi
- PDB-6enq: Structure of human PPAR gamma LBD in complex with Lanifibranor (I... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6enq
TitleStructure of human PPAR gamma LBD in complex with Lanifibranor (IVA337)
ComponentsPeroxisome proliferator-activated receptor gamma
KeywordsTRANSCRIPTION / Nuclear hormone receptor / PPARgamma modulator / Lanifibranor
Function / homology
Function and homology information


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 / 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 ...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 / 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 / WW domain binding / STAT family protein binding / positive regulation of fatty acid metabolic process / response to lipid / negative regulation of SMAD protein signal transduction / 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 / 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 / negative regulation of lipid storage / cellular response to low-density lipoprotein particle stimulus / white fat cell differentiation / negative regulation of BMP signaling pathway / cell fate commitment / positive regulation of cholesterol efflux / negative regulation of mitochondrial fission / positive regulation of fat cell differentiation / negative regulation of osteoblast differentiation / 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 / epithelial cell differentiation / negative regulation of signaling receptor activity / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / hormone-mediated signaling pathway / regulation of cellular response to insulin stimulus / negative regulation of angiogenesis / response to nutrient / negative regulation of miRNA transcription / Regulation of PTEN gene transcription / transcription coregulator binding / fatty acid metabolic process / negative regulation of smooth muscle cell proliferation / positive regulation of apoptotic signaling pathway / negative regulation of transforming growth factor beta receptor signaling pathway / peptide binding / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / regulation of circadian rhythm / placenta development / PPARA activates gene expression / lipid metabolic process / DNA-binding transcription repressor activity, RNA polymerase II-specific / negative regulation of inflammatory response / positive regulation of miRNA transcription / regulation of blood pressure / cellular response to insulin stimulus / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / nuclear receptor activity / rhythmic process / glucose homeostasis / cellular response to hypoxia / double-stranded DNA binding / DNA-binding transcription activator activity, RNA polymerase II-specific / DNA-binding transcription factor binding / sequence-specific DNA binding / nucleic acid binding / cell differentiation / receptor complex / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of gene expression / intracellular membrane-bounded organelle / innate immune response / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of gene expression
Similarity search - Function
Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Peroxisome proliferator-activated receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type ...Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Peroxisome proliferator-activated receptor / : / Retinoid X Receptor / Retinoid X Receptor / 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-BJB / Peroxisome proliferator-activated receptor gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsBoubia, B. / Poupardin, O. / Barth, M. / Amaudrut, J. / Broqua, P. / Tallandier, M. / Zeyer, D.
CitationJournal: J. Med. Chem. / Year: 2018
Title: Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) alpha / gamma / delta Triple Activators: Discovery of Lanifibranor, ...Title: Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) alpha / gamma / delta Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate.
Authors: Boubia, B. / Poupardin, O. / Barth, M. / Binet, J. / Peralba, P. / Mounier, L. / Jacquier, E. / Gauthier, E. / Lepais, V. / Chatar, M. / Ferry, S. / Thourigny, A. / Guillier, F. / Llacer, J. ...Authors: Boubia, B. / Poupardin, O. / Barth, M. / Binet, J. / Peralba, P. / Mounier, L. / Jacquier, E. / Gauthier, E. / Lepais, V. / Chatar, M. / Ferry, S. / Thourigny, A. / Guillier, F. / Llacer, J. / Amaudrut, J. / Dodey, P. / Lacombe, O. / Masson, P. / Montalbetti, C. / Wettstein, G. / Luccarini, J.M. / Legendre, C. / Junien, J.L. / Broqua, P.
History
DepositionOct 6, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 14, 2018Provider: repository / Type: Initial release
Revision 1.1Apr 4, 2018Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Source and taxonomy
Category: citation / entity_src_gen ...citation / entity_src_gen / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_oper_list
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _entity_src_gen.pdbx_host_org_ncbi_taxonomy_id / _entity_src_gen.pdbx_host_org_scientific_name / _pdbx_struct_assembly.details / _pdbx_struct_assembly.oligomeric_count / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_prop.value
Revision 1.2Jan 17, 2024Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Peroxisome proliferator-activated receptor gamma
B: Peroxisome proliferator-activated receptor gamma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,8533
Polymers64,4192
Non-polymers4351
Water3,099172
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1980 Å2
ΔGint1 kcal/mol
Surface area24120 Å2
MethodPISA
Unit cell
Length a, b, c (Å)92.880, 60.000, 117.490
Angle α, β, γ (deg.)90.00, 102.93, 90.00
Int Tables number5
Space group name H-MC121

-
Components

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


Mass: 32209.275 Da / Num. of mol.: 2
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: Chemical ChemComp-BJB / 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloro-indol-2-yl]butanoic acid


Mass: 434.916 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H15ClN2O4S2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 172 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.48 Å3/Da / Density % sol: 50.33 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: Na Citrate 0,9 M 1,2 - propanediol 3,5 % Hepes 0,1 M

-
Data collection

DiffractionMean temperature: 123 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 1, 2005
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. obs: 32992 / % possible obs: 97.6 % / Redundancy: 3.1 % / Biso Wilson estimate: 43 Å2 / Rsym value: 0.064 / Net I/σ(I): 16.5
Reflection shellResolution: 2.2→2.8 Å / Redundancy: 3 % / Mean I/σ(I) obs: 3.5 / Rsym value: 0.349 / % possible all: 94.8

-
Processing

Software
NameVersionClassification
CNX2005refinement
HKL-2000data reduction
SCALEPACKdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1prg

1prg


Resolution: 2.2→50 Å / Cross valid method: FREE R-VALUE
RfactorNum. reflection% reflection
Rfree0.2714 --
Rwork0.2268 --
obs-29908 92.8 %
Refinement stepCycle: LAST / Resolution: 2.2→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4023 0 28 172 4223

+
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