[English] 日本語
Yorodumi
- PDB-3kmg: The X-ray Crystal Structure of PPAR-gamma in Complex with an Indo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3kmg
TitleThe X-ray Crystal Structure of PPAR-gamma in Complex with an Indole Derivative Modulator, GSK538, and an SRC-1 Peptide
Components
  • Peroxisome proliferator-activated receptor gamma
  • Steroid Receptor Coactivator-1Nuclear receptor coactivator 1
KeywordsTRANSCRIPTION / PPAR-gamma / Peroxisome proliferator-activated receptor / Telmisartan / Diabetes / Modulator / Activator / Diabetes mellitus / Disease mutation / DNA-binding / Metal-binding / Nucleus / Obesity / Phosphoprotein / Receptor / Transcription regulation / Zinc-finger
Function / homology
Function and homology information


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 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 ...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 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 / 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 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 / negative regulation of BMP signaling pathway / white fat cell differentiation / negative regulation of mitochondrial fission / positive regulation of cholesterol efflux / retinoic acid receptor signaling pathway / positive regulation of fat cell differentiation / negative regulation of osteoblast differentiation / cell fate commitment / positive regulation of DNA binding / BMP signaling pathway / long-chain fatty acid transport / nuclear retinoid X receptor binding / negative regulation of signaling receptor activity / regulation of cellular response to insulin stimulus / cell maturation / epithelial cell differentiation / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / hormone-mediated signaling pathway / negative regulation of angiogenesis / response to nutrient / negative regulation of miRNA transcription / fatty acid metabolic process / negative regulation of MAP kinase activity / Regulation of PTEN gene transcription / transcription coregulator binding / placenta development / negative regulation of smooth muscle cell proliferation / peptide binding / negative regulation of transforming growth factor beta receptor signaling pathway / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / regulation of circadian rhythm / lipid metabolic process / PPARA activates gene expression / regulation of blood pressure / DNA-binding transcription repressor activity, RNA polymerase II-specific / positive regulation of DNA-binding transcription factor activity / negative regulation of inflammatory response / positive regulation of miRNA transcription / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / cellular response to insulin stimulus / RNA polymerase II transcription regulator complex / activation of cysteine-type endopeptidase activity involved in apoptotic process / 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 / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / intracellular membrane-bounded organelle / innate immune response / negative regulation of DNA-templated transcription / chromatin binding
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 / Zinc finger, C4 type (two domains) ...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-538 / Peroxisome proliferator-activated receptor gamma
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsGampe, R.
CitationJournal: TO BE PUBLISHED
Title: Synthesis and biological activities of novel indole derivatives as potent and selective PPAR-gamma modulators
Authors: Lamotte, Y. / Martres, P. / Faucher, N. / Laroze, A. / Grillot, D. / Ancellin, N. / Saintillan, Y. / Beneton, V. / Gampe, R.
History
DepositionNov 10, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 12, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Nov 1, 2017Group: Refinement description / Category: software
Revision 1.3Jan 24, 2018Group: Database references / Category: citation_author / Item: _citation_author.name
Revision 1.4Sep 6, 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_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Mar 13, 2024Group: Source and taxonomy / Structure summary / Category: entity / pdbx_entity_src_syn / Item: _entity.details

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Peroxisome proliferator-activated receptor gamma
B: Steroid Receptor Coactivator-1
D: Peroxisome proliferator-activated receptor gamma
E: Steroid Receptor Coactivator-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,8826
Polymers67,8494
Non-polymers1,0332
Water3,675204
1
A: Peroxisome proliferator-activated receptor gamma
B: Steroid Receptor Coactivator-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4413
Polymers33,9242
Non-polymers5171
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1090 Å2
ΔGint-10 kcal/mol
Surface area12890 Å2
MethodPISA
2
D: Peroxisome proliferator-activated receptor gamma
E: Steroid Receptor Coactivator-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4413
Polymers33,9242
Non-polymers5171
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1250 Å2
ΔGint-10 kcal/mol
Surface area13350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)83.335, 84.158, 96.425
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: 31094.135 Da / Num. of mol.: 2 / Fragment: UNP residues 234-505
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPARG, NR1C3 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P37231
#2: Protein/peptide Steroid Receptor Coactivator-1 / Nuclear receptor coactivator 1


Mass: 2830.208 Da / Num. of mol.: 2 / Source method: obtained synthetically / Details: synthetic peptide compound
#3: Chemical ChemComp-538 / 4'-[(2,3-dimethyl-5-{[(1S)-1-phenylpropyl]carbamoyl}-1H-indol-1-yl)methyl]biphenyl-2-carboxylic acid


Mass: 516.629 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32N2O3 / Details: synthetic organic compound
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 204 / 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: 2.49 Å3/Da / Density % sol: 50.64 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: Diffraction grade crystals grew in 7-14 days at 22C using 2uL vapor diffused hanging drops made with 1uL of the complex and 1uL of the well solution comprised of 14% PEG4K, 0.2M NaSCN and 0. ...Details: Diffraction grade crystals grew in 7-14 days at 22C using 2uL vapor diffused hanging drops made with 1uL of the complex and 1uL of the well solution comprised of 14% PEG4K, 0.2M NaSCN and 0.1M Bis-tris pH 6.5., VAPOR DIFFUSION, HANGING DROP, temperature 295K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jul 17, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.1→50 Å / Num. all: 40155 / Num. obs: 39982 / % possible obs: 99.6 % / Observed criterion σ(I): -3 / Redundancy: 7.2 % / Rmerge(I) obs: 0.038 / Net I/σ(I): 45.7
Reflection shellResolution: 2.1→2.18 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.427 / Mean I/σ(I) obs: 3.3 / % possible all: 96.8

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
REFMAC5.5.0053refinement
PDB_EXTRACT3.005data extraction
JDirectordata collection
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: RCSB ENTRY 1fm9 chain D

1fm9


Resolution: 2.1→41.85 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.935 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 10.395 / SU ML: 0.127 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.199 / ESU R Free: 0.168 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.23014 1247 3.1 %RANDOM
Rwork0.19812 ---
obs0.19915 38828 99.53 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 40.254 Å2
Baniso -1Baniso -2Baniso -3
1-0.01 Å20 Å20 Å2
2---0.01 Å20 Å2
3----0.01 Å2
Refinement stepCycle: LAST / Resolution: 2.1→41.85 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4239 0 78 204 4521
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0224453
X-RAY DIFFRACTIONr_bond_other_d0.0010.022986
X-RAY DIFFRACTIONr_angle_refined_deg1.2562.0066030
X-RAY DIFFRACTIONr_angle_other_deg0.88737344
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0025557
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.95224.919185
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.98515810
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.3651519
X-RAY DIFFRACTIONr_chiral_restr0.0680.2699
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.024873
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02864
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_it0.491.52735
X-RAY DIFFRACTIONr_mcbond_other0.091.51098
X-RAY DIFFRACTIONr_mcangle_it0.92224410
X-RAY DIFFRACTIONr_scbond_it1.42531718
X-RAY DIFFRACTIONr_scangle_it2.324.51610
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.1→2.154 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.281 68 -
Rwork0.251 2759 -
obs--95.8 %
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)
12.22580.05410.77251.512-0.68683.85020.0607-0.0343-0.00070.0383-0.1397-0.12840.05890.10020.079-0.1962-0.00510.0409-0.21890.0036-0.121215.43625.5235.316
22.60830.5285-0.89322.31610.11172.3635-0.0197-0.23340.16540.18110.01050.1434-0.20180.24640.0093-0.07460.01880.0147-0.1474-0.0609-0.13541.42955.637-2.755
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A209 - 476
2X-RAY DIFFRACTION1B686 - 695
3X-RAY DIFFRACTION2D208 - 476
4X-RAY DIFFRACTION2E682 - 698

+
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