[English] 日本語
Yorodumi
- PDB-3s9s: Ligand binding domain of PPARgamma complexed with a benzimidazole... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3s9s
TitleLigand binding domain of PPARgamma complexed with a benzimidazole partial agonist
Components
  • Nuclear receptor coactivator 1
  • Peroxisome proliferator-activated receptor gamma
KeywordsTRANSCRIPTION / PPAR / NUCLEAR RECEPTOR
Function / homology
Function and homology information


labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / 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 / positive regulation of female receptivity / negative regulation of extracellular matrix assembly ...labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / 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 / positive regulation of female receptivity / 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 / 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 / hypothalamus development / STAT family protein binding / male mating behavior / 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 / 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 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 / estrous cycle / negative regulation of BMP signaling pathway / cellular response to Thyroglobulin triiodothyronine / white fat cell differentiation / negative regulation of mitochondrial fission / Synthesis of bile acids and bile salts / positive regulation of cholesterol efflux / 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 / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / long-chain fatty acid transport / nuclear retinoid X receptor binding / response to retinoic acid / negative regulation of signaling receptor activity / histone acetyltransferase activity / cell maturation / regulation of cellular response to insulin stimulus / Recycling of bile acids and salts / histone acetyltransferase / cellular response to hormone 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 / RORA activates gene expression / lactation / positive regulation of neuron differentiation / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / cerebellum development / negative regulation of angiogenesis / response to nutrient / BMAL1:CLOCK,NPAS2 activates circadian gene expression / fatty acid metabolic process / Activation of gene expression by SREBF (SREBP) / SUMOylation of transcription cofactors / nuclear receptor coactivator activity / negative regulation of miRNA transcription / placenta development / response to progesterone / negative regulation of MAP kinase activity / Regulation of PTEN gene transcription / transcription coregulator binding / nuclear estrogen receptor binding / nuclear receptor binding / hippocampus development / negative regulation of smooth muscle cell proliferation / peptide binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / negative regulation of transforming growth factor beta receptor signaling pathway / Heme signaling / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II
Similarity search - Function
Nuclear receptor coactivator 1 / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Peroxisome proliferator-activated receptor / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator ...Nuclear receptor coactivator 1 / Peroxisome proliferator-activated receptor gamma / Peroxisome proliferator-activated receptor gamma, N-terminal / PPAR gamma N-terminal region / Peroxisome proliferator-activated receptor / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator / DUF1518 / Nuclear receptor coactivator, receptor-binding domain / Nuclear receptor coactivator / Steroid receptor coactivator / Unstructured region on nuclear receptor coactivator protein / PAS domain / Helix-loop-helix DNA-binding domain superfamily / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / Nuclear receptor coactivator, interlocking / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / PAS domain superfamily / 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-M0T / Peroxisome proliferator-activated receptor gamma / Nuclear receptor coactivator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.55 Å
AuthorsLambert, M.H. / Xu, R.X.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2011
Title: Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARgamma partial agonist.
Authors: Sime, M. / Allan, A.C. / Chapman, P. / Fieldhouse, C. / Giblin, G.M. / Healy, M.P. / Lambert, M.H. / Leesnitzer, L.M. / Lewis, A. / Merrihew, R.V. / Rutter, R.A. / Sasse, R. / Shearer, B.G. ...Authors: Sime, M. / Allan, A.C. / Chapman, P. / Fieldhouse, C. / Giblin, G.M. / Healy, M.P. / Lambert, M.H. / Leesnitzer, L.M. / Lewis, A. / Merrihew, R.V. / Rutter, R.A. / Sasse, R. / Shearer, B.G. / Wilson, T.M. / Xu, R.X. / Virley, D.J.
History
DepositionJun 2, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 6, 2012Provider: repository / Type: Initial release
Revision 1.1Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Peroxisome proliferator-activated receptor gamma
B: Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,6703
Polymers34,2182
Non-polymers4521
Water93752
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1090 Å2
ΔGint-9 kcal/mol
Surface area12970 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.086, 88.754, 122.605
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

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


Mass: 32583.859 Da / Num. of mol.: 1 / Fragment: LIGAND BINDING DOMAIN (RESIDUES 234-505)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1C3, PPARG / Plasmid: PRSETA / Production host: Escherichia coli (E. coli) / Strain (production host): BL21DE3 / References: UniProt: P37231
#2: Protein/peptide Nuclear receptor coactivator 1 /


Mass: 1633.916 Da / Num. of mol.: 1 / Fragment: LXXLL MOTIF 4 (RESIDUES 685-697) / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15788
#3: Chemical ChemComp-M0T / 1-(3,4-dichlorobenzyl)-2-methyl-N-[(1R)-1-phenylpropyl]-1H-benzimidazole-5-carboxamide


Mass: 452.376 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H23Cl2N3O
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 52 / 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: 2.23 Å3/Da / Density % sol: 44.83 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 100MM HEPES, 1.4M SODIUM CITRATE, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jun 9, 2007
RadiationMonochromator: SI 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.55→61.3 Å / Num. all: 9418 / Num. obs: 9418 / % possible obs: 95.9 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 5.6 % / Rmerge(I) obs: 0.058 / Net I/σ(I): 47.6
Reflection shellResolution: 2.55→2.61 Å / Redundancy: 5 % / Rmerge(I) obs: 0.44 / Mean I/σ(I) obs: 5 / % possible all: 85

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
AMoREphasing
REFMAC5.5.0109refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 2POB

2pob


Resolution: 2.55→61.3 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.905 / SU B: 28.847 / SU ML: 0.301 / Cross valid method: THROUGHOUT / σ(F): 2 / ESU R Free: 0.36 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.284 477 4.8 %RANDOM
Rwork0.224 ---
obs0.227 9418 95.9 %-
all-9418 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 71.789 Å2
Baniso -1Baniso -2Baniso -3
1-1.9 Å20 Å20 Å2
2--1.41 Å20 Å2
3----3.31 Å2
Refinement stepCycle: LAST / Resolution: 2.55→61.3 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2095 0 31 52 2178
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0222174
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.1582.0062939
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.6785263
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.59724.83189
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.84115387
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.106158
X-RAY DIFFRACTIONr_chiral_restr0.0690.2344
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0211653
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.3791.51334
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.70922143
X-RAY DIFFRACTIONr_scbond_it1.1023840
X-RAY DIFFRACTIONr_scangle_it1.7994.5796
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.55→2.62 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.436 32 -
Rwork0.313 614 -
obs--85.22 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.70540.3620.0294.0391.21384.1737-0.32340.3298-0.0313-0.71630.4927-0.2230.20070.3127-0.16920.2732-0.15630.03740.4686-0.02710.2901-22.98411.502-14.795
231.42695.5352-0.734938.0571-3.74348.5971-1.15232.2528-1.1826-2.26881.0214-1.46010.65582.46910.13090.3262-0.23050.19451.5004-0.26580.6484-3.39614.013-14.06
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A208 - 476
2X-RAY DIFFRACTION2B686 - 695

+
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