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==Crystal structure of hPPARgamma ligand binding domain complexed with rosiglitazone-based fluorescence probe== | ==Crystal structure of hPPARgamma ligand binding domain complexed with rosiglitazone-based fluorescence probe== | ||
<StructureSection load='7efq' size='340' side='right'caption='[[7efq]]' scene=''> | <StructureSection load='7efq' size='340' side='right'caption='[[7efq]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EFQ FirstGlance]. <br> | <table><tr><td colspan='2'>[[7efq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EFQ FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7efq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7efq OCA], [https://pdbe.org/7efq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7efq RCSB], [https://www.ebi.ac.uk/pdbsum/7efq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7efq ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J3F:(5S)-5-[[4-[2-[[7-(diethylamino)-2-oxidanylidene-chromen-4-yl]-methyl-amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione'>J3F</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7efq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7efq OCA], [https://pdbe.org/7efq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7efq RCSB], [https://www.ebi.ac.uk/pdbsum/7efq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7efq ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref> Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[https://omim.org/entry/604367 604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref> Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a molecular target of metabolic syndrome and inflammatory disease. PPARgamma is an important nuclear receptor and numerous PPARgamma ligands were developed to date; thus, efficient assay methods are important. Here, we investigated the incorporation of 7-diethylamino coumarin into the PPARgamma agonist rosiglitazone and used the compound in a binding assay for PPARgamma. PPARgamma-ligand-incorporated 7-methoxycoumarin, 1, showed weak fluorescence intensity in a previous report. We synthesized PPARgamma-ligand-incorporating coumarin, 2, in this report, and it enhanced the fluorescence intensity. The PPARgamma ligand 2 maintained the rosiglitazone activity. The obtained partial agonist 6 appeared to act through a novel mechanism. The fluorescence intensity of 2 and 6 increased by binding to the ligand binding domain (LBD) of PPARgamma and the affinity of reported PPARgamma ligands were evaluated using the probe. | |||
Synthesis of a Coumarin-Based PPARgamma Fluorescence Probe for Competitive Binding Assay.,Yoshikawa C, Ishida H, Ohashi N, Itoh T Int J Mol Sci. 2021 Apr 14;22(8). pii: ijms22084034. doi: 10.3390/ijms22084034. PMID:33919837<ref>PMID:33919837</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7efq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ishida H]] | [[Category: Ishida H]] | ||