[English] 日本語
Yorodumi
- PDB-2p54: a crystal structure of PPAR alpha bound with SRC1 peptide and GW735 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2p54
Titlea crystal structure of PPAR alpha bound with SRC1 peptide and GW735
Components
  • Nuclear receptor coactivator 1
  • Peroxisome proliferator-activated receptor alpha
KeywordsTRANSCRIPTION / PPAR alpha GW735 SRC1 agonist HDLc
Function / homology
Function and homology information


positive regulation of transformation of host cell by virus / regulation of fatty acid transport / enamel mineralization / negative regulation of cell growth involved in cardiac muscle cell development / positive regulation of fatty acid oxidation / regulation of fatty acid metabolic process / cellular response to fructose stimulus / regulation of cellular ketone metabolic process / behavioral response to nicotine / negative regulation of appetite ...positive regulation of transformation of host cell by virus / regulation of fatty acid transport / enamel mineralization / negative regulation of cell growth involved in cardiac muscle cell development / positive regulation of fatty acid oxidation / regulation of fatty acid metabolic process / cellular response to fructose stimulus / regulation of cellular ketone metabolic process / behavioral response to nicotine / negative regulation of appetite / lipoprotein metabolic process / positive regulation of fatty acid beta-oxidation / negative regulation of hepatocyte apoptotic process / mitogen-activated protein kinase kinase kinase binding / negative regulation of leukocyte cell-cell adhesion / labyrinthine layer morphogenesis / ubiquitin conjugating enzyme binding / regulation of thyroid hormone receptor signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / negative regulation of glycolytic process / positive regulation of female receptivity / negative regulation of sequestering of triglyceride / nuclear steroid receptor activity / DNA-binding transcription activator activity / hypothalamus development / nitric oxide metabolic process / positive regulation of fatty acid metabolic process / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / positive regulation of ATP biosynthetic process / NFAT protein binding / negative regulation of cholesterol storage / negative regulation of macrophage derived foam cell differentiation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to Thyroglobulin triiodothyronine / estrous cycle / Synthesis of bile acids and bile salts / negative regulation of cytokine production involved in inflammatory response / epidermis development / phosphatase binding / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / positive regulation of lipid biosynthetic process / nuclear retinoid X receptor binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / negative regulation of reactive oxygen species biosynthetic process / response to retinoic acid / histone acetyltransferase activity / Recycling of bile acids and salts / histone acetyltransferase / cellular response to hormone stimulus / negative regulation of signaling receptor activity / positive regulation of gluconeogenesis / MDM2/MDM4 family protein binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / positive regulation of adipose tissue development / RORA activates gene expression / peroxisome proliferator activated receptor signaling pathway / negative regulation of blood pressure / positive regulation of neuron differentiation / lactation / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / cellular response to starvation / regulation of cellular response to insulin stimulus / cerebellum development / response to nutrient / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / negative regulation of miRNA transcription / nuclear receptor coactivator activity / fatty acid metabolic process / gluconeogenesis / response to progesterone / nuclear receptor binding / hippocampus development / nuclear estrogen receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / negative regulation of transforming growth factor beta receptor signaling pathway / circadian regulation of gene expression / wound healing / Heme signaling / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / response to insulin / Transcriptional activation of mitochondrial biogenesis / regulation of circadian rhythm / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / transcription coactivator binding / DNA-binding transcription repressor activity, RNA polymerase II-specific / negative regulation of inflammatory response / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / nuclear receptor activity / male gonad development
Similarity search - Function
Peroxisome proliferator-activated receptor alpha / Nuclear receptor coactivator 1 / 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 ...Peroxisome proliferator-activated receptor alpha / Nuclear receptor coactivator 1 / 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 / : / Nuclear receptor coactivator, interlocking / 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. / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / Retinoid X Receptor / Retinoid X Receptor / PAS 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-735 / Peroxisome proliferator-activated receptor alpha / Nuclear receptor coactivator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.79 Å
AuthorsXu, R.X. / Xu, H.E. / Sierra, M.L. / Montana, V.G. / Lambert, M.H. / Pianetti, P.M.
CitationJournal: J.Med.Chem. / Year: 2007
Title: Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPAR Agonists. 1.Discovery of a Novel Series of Potent HDLc Raising Agents.
Authors: Sierra, M.L. / Beneton, V. / Boullay, A.B. / Boyer, T. / Brewster, A. / Donche, F. / Forest, M.C. / Fouchet, M.H. / Gellibert, F.J. / Grillot, D.A. / Lambert, M.H. / Laroze, A. / Grumelec, C. ...Authors: Sierra, M.L. / Beneton, V. / Boullay, A.B. / Boyer, T. / Brewster, A. / Donche, F. / Forest, M.C. / Fouchet, M.H. / Gellibert, F.J. / Grillot, D.A. / Lambert, M.H. / Laroze, A. / Grumelec, C.L. / Linget, J.M. / Montana, V.G. / Nguyen, V.L. / Nicodeme, E. / Patel, V. / Penfornis, A. / Pineau, O. / Pohin, D. / Potvain, F. / Paulain, G. / Ruault, C.B. / Saunders, M. / Toum, J. / Xu, H.E. / Xu, R.X. / Pianetti, P.M.
History
DepositionMar 14, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 24, 2007Provider: repository / Type: Initial release
Revision 1.1Mar 13, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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
Revision 1.4Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)32,2683
Polymers31,7892
Non-polymers4781
Water4,828268
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)61.263, 103.535, 49.850
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

#1: Protein Peroxisome proliferator-activated receptor alpha / PPAR-alpha


Mass: 30270.402 Da / Num. of mol.: 1 / Fragment: PPAR alpha
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPARA, NR1C1, PPAR / Production host: Escherichia coli (E. coli) / References: UniProt: Q07869
#2: Protein/peptide Nuclear receptor coactivator 1 / NCoA-1 / Steroid receptor coactivator 1 / SRC-1 / RIP160 / Protein Hin-2 / Renal carcinoma antigen NY-REN-52


Mass: 1518.828 Da / Num. of mol.: 1 / Fragment: SRC1 peptide / Source method: obtained synthetically / Details: This sequence occurs naturally in humans / References: UniProt: Q15788, histone acetyltransferase
#3: Chemical ChemComp-735 / 2-METHYL-2-(4-{[({4-METHYL-2-[4-(TRIFLUOROMETHYL)PHENYL]-1,3-THIAZOL-5-YL}CARBONYL)AMINO]METHYL}PHENOXY)PROPANOIC ACID


Mass: 478.484 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H21F3N2O4S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 268 / 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: 50.52 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 7% PEG 3350, 200 mM NaF, 12% 2,5-hexanediol, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 295K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: Jul 5, 2001
RadiationMonochromator: Si 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.79→20 Å / Num. all: 30633 / Num. obs: 30145 / % possible obs: 98 % / Observed criterion σ(F): 5 / Observed criterion σ(I): 5.24 / Redundancy: 7.1 % / Biso Wilson estimate: 3.2 Å2 / Rmerge(I) obs: 0.045 / Rsym value: 0.045 / Net I/σ(I): 39.45
Reflection shellResolution: 1.79→1.86 Å / Redundancy: 7.5 % / Rmerge(I) obs: 0.35 / Mean I/σ(I) obs: 5.2 / Num. unique all: 2848 / Rsym value: 0.35 / % possible all: 95.8

-
Processing

Software
NameClassification
HKL-2000data collection
AMoREphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: apo PPAR alpha

Resolution: 1.79→20 Å / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber / Details: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.227 1761 -RANDOM
Rwork0.204 ---
all0.205 30633 --
obs0.204 29552 96.5 %-
Displacement parametersBiso mean: 27 Å2
Baniso -1Baniso -2Baniso -3
1--0.015 Å20 Å20 Å2
2--0.01 Å20 Å2
3---0.005 Å2
Refinement stepCycle: LAST / Resolution: 1.79→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2196 0 53 268 2517
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_angle_deg1.287
X-RAY DIFFRACTIONc_bond_d0.005

+
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://pdbjlc1.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