+Open data
-Basic information
Entry | Database: PDB / ID: 4e4k | ||||||
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Title | Crystal Structure of PPARgamma with the ligand JO21 | ||||||
Components | Peroxisome proliferator-activated receptor gamma | ||||||
Keywords | TRANSCRIPTION / bundle of alpha-helices and a small four-stranded beta-sheet / transcription factor | ||||||
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 / positive regulation of vascular associated smooth muscle cell apoptotic process / macrophage derived foam cell differentiation / 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 / negative regulation of blood vessel endothelial cell migration / lipid homeostasis / negative regulation of vascular associated smooth muscle cell proliferation / R-SMAD binding / monocyte differentiation / positive regulation of cholesterol efflux / negative regulation of macrophage derived foam cell differentiation / cellular response to low-density lipoprotein particle stimulus / negative regulation of lipid storage / negative regulation of BMP signaling pathway / white fat cell differentiation / negative regulation of mitochondrial fission / positive regulation of fat cell differentiation / negative regulation of osteoblast differentiation / long-chain fatty acid transport / retinoic acid receptor signaling pathway / positive regulation of DNA binding / cell fate commitment / BMP signaling pathway / nuclear retinoid X receptor binding / negative regulation of signaling receptor activity / regulation of cellular response to insulin stimulus / cell maturation / positive regulation of adipose tissue development / epithelial cell differentiation / peroxisome proliferator activated receptor signaling pathway / hormone-mediated signaling pathway / negative regulation of angiogenesis / response to nutrient / negative regulation of MAP kinase activity / fatty acid metabolic process / negative regulation of miRNA transcription / placenta development / Regulation of PTEN gene transcription / negative regulation of smooth muscle cell proliferation / transcription coregulator binding / peptide binding / negative regulation of transforming growth factor beta receptor signaling pathway / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / lipid metabolic process / regulation of circadian rhythm / PPARA activates gene expression / negative regulation of inflammatory response / DNA-binding transcription repressor activity, RNA polymerase II-specific / regulation of blood pressure / Transcriptional regulation of white adipocyte differentiation / positive regulation of miRNA transcription / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / cellular response to insulin stimulus / activation of cysteine-type endopeptidase activity involved in apoptotic process / rhythmic process / : / nuclear receptor activity / positive regulation of DNA-binding transcription factor activity / 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 / cell differentiation / nucleic acid binding / 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 / innate immune response / intracellular membrane-bounded organelle / negative regulation of DNA-templated transcription / chromatin binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å | ||||||
Authors | Pochetti, G. / Montanari, R. / Loiodice, F. / Fracchiolla, G. / Laghezza, A. / Carbonara, G. / Piemontese, L. / Lavecchia, A. / Novellino, E. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: New 2-(Aryloxy)-3-phenylpropanoic Acids as Peroxisome Proliferator-Activated Receptor alpha/gamma Dual Agonists Able To Upregulate Mitochondrial Carnitine Shuttle System Gene Expression. Authors: Laghezza, A. / Pochetti, G. / Lavecchia, A. / Fracchiolla, G. / Faliti, S. / Piemontese, L. / Di Giovanni, C. / Iacobazzi, V. / Infantino, V. / Montanari, R. / Capelli, D. / Tortorella, P. / Loiodice, F. #1: Journal: J.Med.Chem. / Year: 2008 Title: Crystal structure of the peroxisome proliferator-activated receptor gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design Authors: Montanari, R. / Saccoccia, F. / Scotti, E. / Crestani, M. / Godio, C. / Gilardi, F. / Loiodice, F. / Fracchiolla, G. / Laghezza, A. / Tortorella, P. / Lavecchia, A. / Novellino, E. / Mazza, ...Authors: Montanari, R. / Saccoccia, F. / Scotti, E. / Crestani, M. / Godio, C. / Gilardi, F. / Loiodice, F. / Fracchiolla, G. / Laghezza, A. / Tortorella, P. / Lavecchia, A. / Novellino, E. / Mazza, F. / Aschi, M. / Pochetti, G. #2: Journal: J.Biol.Chem. / Year: 2008 Title: T2384, a novel antidiabetic agent with unique peroxisome proliferator-activated receptor gamma binding properties Authors: Li, Y. / Wang, Z. / Furukawa, N. / Escaron, P. / Weiszmann, J. / Lee, G. / Lindstrom, M. / Liu, J. / Liu, X. / Xu, H. / Plotnikova, O. / Prasad, V. / Walker, N. / Learned, R.M. / Chen, J.L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4e4k.cif.gz | 122.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4e4k.ent.gz | 96.1 KB | Display | PDB format |
PDBx/mmJSON format | 4e4k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e4/4e4k ftp://data.pdbj.org/pub/pdb/validation_reports/e4/4e4k | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 32693.824 Da / Num. of mol.: 2 / Fragment: Ligand binding domain (UNP residues 223-505) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PPARG, NR1C3 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / References: UniProt: P37231 #2: Chemical | #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.57 Å3/Da / Density % sol: 52.08 % |
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Crystal grow | Temperature: 293 K / pH: 8 Details: 0.8M NACITRATE, 0.15M TRIS, PH8.0, VAPOR DIFFUSION, SITTING DROP, temperature 293 KK |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.873 |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: May 6, 2010 |
Radiation | Monochromator: SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.873 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→45 Å / Num. obs: 23188 / % possible obs: 100 % / Observed criterion σ(I): 0 / Redundancy: 3.8 % / Biso Wilson estimate: 53.16 Å2 / Rmerge(I) obs: 0.065 / Net I/σ(I): 12.4 |
Reflection shell | Resolution: 2.5→2.64 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.449 / Mean I/σ(I) obs: 3 / % possible all: 100 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→10 Å / σ(F): 0 / Stereochemistry target values: Engh & Huber Details: THE ELECTRON DENSITY IN THE REGION OF THE LIGANDS RRG 501 AND RRG 502 WAS WEAK. IT IS POSSIBLE THAT THE LIGANDS ARE DISORDERED. THE DETAILS OF LIGAND MODELING ARE DESCRIBED IN THE MANUSCRIPT.
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Refinement step | Cycle: LAST / Resolution: 2.5→10 Å
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Refine LS restraints |
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