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- PDB-8b93: Crystal structure of PPARG and NCOR2 with an inverse agonist (com... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8b93 | ||||||
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Title | Crystal structure of PPARG and NCOR2 with an inverse agonist (compound 15b) | ||||||
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![]() | TRANSCRIPTION / nuclear hormone receptor transcription factor | ||||||
Function / homology | ![]() Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / regulation of cellular ketone metabolic process / nuclear glucocorticoid receptor 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 / Notch binding ...Loss of MECP2 binding ability to the NCoR/SMRT complex / negative regulation of androgen receptor signaling pathway / regulation of cellular ketone metabolic process / nuclear glucocorticoid receptor 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 / Notch binding / 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 / arachidonate binding / positive regulation of low-density lipoprotein receptor activity / positive regulation of adiponectin secretion / lipoprotein transport / negative regulation of sequestering of triglyceride / DNA binding domain binding / macrophage derived foam cell differentiation / STAT family protein binding / positive regulation of vascular associated smooth muscle cell apoptotic process / positive regulation of fatty acid metabolic process / response to lipid / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of SMAD protein signal transduction / LBD domain binding / Notch-HLH transcription pathway / 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 / Regulation of MECP2 expression and activity / negative regulation of blood vessel endothelial cell migration / negative regulation of lipid storage / cellular response to low-density lipoprotein particle stimulus / white fat cell differentiation / negative regulation of BMP signaling pathway / estrous cycle / negative regulation of mitochondrial fission / positive regulation of cholesterol efflux / positive regulation of fat cell differentiation / negative regulation of osteoblast differentiation / retinoic acid receptor signaling pathway / cell fate commitment / BMP signaling pathway / long-chain fatty acid transport / nuclear retinoid X receptor binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / cell maturation / negative regulation of signaling receptor activity / 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 / transcription repressor complex / lactation / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / regulation of cellular response to insulin stimulus / negative regulation of angiogenesis / cerebellum development / response to nutrient / SUMOylation of transcription cofactors / negative regulation of miRNA transcription / negative regulation of MAP kinase activity / fatty acid metabolic process / Regulation of PTEN gene transcription / transcription coregulator binding / HDACs deacetylate histones / Downregulation of SMAD2/3:SMAD4 transcriptional activity / negative regulation of smooth muscle cell proliferation / negative regulation of transforming growth factor beta receptor signaling pathway / peptide binding / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / placenta development / regulation of circadian rhythm / PPARA activates gene expression / lipid metabolic process / Cytoprotection by HMOX1 / NOTCH1 Intracellular Domain Regulates Transcription / positive regulation of DNA-binding transcription factor activity / DNA-binding transcription repressor activity, RNA polymerase II-specific / histone deacetylase binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / regulation of blood pressure / negative regulation of inflammatory response / positive regulation of miRNA transcription / nuclear matrix / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Friberg, A. / Orsi, D.L. / Pook, E. / Siegel, S. / Lemke, C.T. / Stellfeld, T. / Puetter, V. / Goldstein, J. | ||||||
Funding support | 1items
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![]() | ![]() Title: Discovery and characterization of orally bioavailable 4-chloro-6-fluoroisophthalamides as covalent PPARG inverse-agonists. Authors: Orsi, D.L. / Ferrara, S.J. / Siegel, S. / Friberg, A. / Bouche, L. / Pook, E. / Lienau, P. / Bluck, J.P. / Lemke, C.T. / Akcay, G. / Stellfeld, T. / Meyer, H. / Putter, V. / Holton, S.J. / ...Authors: Orsi, D.L. / Ferrara, S.J. / Siegel, S. / Friberg, A. / Bouche, L. / Pook, E. / Lienau, P. / Bluck, J.P. / Lemke, C.T. / Akcay, G. / Stellfeld, T. / Meyer, H. / Putter, V. / Holton, S.J. / Korr, D. / Jerchel-Furau, I. / Pantelidou, C. / Strathdee, C.A. / Meyerson, M. / Eis, K. / Goldstein, J.T. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 118.6 KB | Display | ![]() |
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PDB format | ![]() | 90 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8b8wC ![]() 8b8xC ![]() 8b8yC ![]() 8b8zC ![]() 8b90C ![]() 8b91C ![]() 8b92C ![]() 8b94C ![]() 8b95C C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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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: 31862.994 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein/peptide | Mass: 2638.073 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) ![]() #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.26 Å3/Da / Density % sol: 45.54 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: PEG 3350 20%, HCOONa 0.2 M |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 1, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 2.21→45.53 Å / Num. obs: 29412 / % possible obs: 91.8 % / Redundancy: 5.5 % / CC1/2: 0.971 / Rrim(I) all: 0.334 / Net I/σ(I): 3.79 |
Reflection shell | Resolution: 2.21→2.34 Å / Redundancy: 5.3 % / Mean I/σ(I) obs: 1.6 / Num. unique obs: 4613 / CC1/2: 0.625 / Rrim(I) all: 1.374 / % possible all: 90.8 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: internal Resolution: 2.21→45.53 Å / Cor.coef. Fo:Fc: 0.922 / Cor.coef. Fo:Fc free: 0.825 / SU B: 15.593 / SU ML: 0.356 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.39 / ESU R Free: 0.346 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 113.7 Å2 / Biso mean: 42.357 Å2 / Biso min: 19.7 Å2
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Refinement step | Cycle: final / Resolution: 2.21→45.53 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.21→2.267 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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