3v9v: Difference between revisions
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<StructureSection load='3v9v' size='340' side='right'caption='[[3v9v]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='3v9v' size='340' side='right'caption='[[3v9v]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3v9v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3v9v]] 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=3V9V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V9V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21L:METHYL+3-{4-[({[(9AS)-8-ACETYL-1,7-DIHYDROXY-3-METHOXY-9A-METHYL-9-OXO-9,9A-DIHYDRODIBENZO[B,D]FURAN-4-YL]CARBONYL}AMINO)METHYL]NAPHTHALEN-2-YL}PROPANOATE'>21L</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21L:METHYL+3-{4-[({[(9AS)-8-ACETYL-1,7-DIHYDROXY-3-METHOXY-9A-METHYL-9-OXO-9,9A-DIHYDRODIBENZO[B,D]FURAN-4-YL]CARBONYL}AMINO)METHYL]NAPHTHALEN-2-YL}PROPANOATE'>21L</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=3v9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v9v OCA], [https://pdbe.org/3v9v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v9v RCSB], [https://www.ebi.ac.uk/pdbsum/3v9v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v9v ProSAT]</span></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=3v9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v9v OCA], [https://pdbe.org/3v9v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v9v RCSB], [https://www.ebi.ac.uk/pdbsum/3v9v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v9v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hanzawa | [[Category: Hanzawa H]] | ||
[[Category: Matsui | [[Category: Matsui Y]] | ||
Latest revision as of 15:17, 8 November 2023
Crystal structure of the PPARgamma-LBD complexed with a cercosporamide derivative modulatorCrystal structure of the PPARgamma-LBD complexed with a cercosporamide derivative modulator
Structural highlights
DiseasePPARG_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: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.[1] Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM: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.[2] [3] Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM: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. FunctionPPARG_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.[4] [5] [6] Publication Abstract from PubMedPeroxisome proliferator-activated receptor gamma (PPARgamma) is a potential drug target for treating type 2 diabetes. The selective PPARgamma modulators (SPPARMs), which partially activate the PPARgamma transcriptional activity, are considered to improve the plasma glucose level with attenuated PPARgamma related adverse effects. However, the relationships between desired pharmacological profiles and ligand specific PPARgamma transcriptional profiles have been unclear. And there is also little knowledge of how to control ligand specific PPARgamma transcriptional profiles. Herein, we present synthesis of novel derivatives containing substituent at naphthalene C3 position of compound 1. The novel derivatives showed various maximal efficacies as PPARgamma partial agonist. Substituents at the naphthalene C3 position of (-)-Cercosporamide derivatives significantly affect the maximal efficacy as PPARgamma partial agonists.,Furukawa A, Arita T, Fukuzaki T, Satoh S, Mori M, Honda T, Matsui Y, Wakabayashi K, Hayashi S, Araki K, Ohsumi J Bioorg Med Chem Lett. 2012 Feb 1;22(3):1348-51. Epub 2011 Dec 16. PMID:22225641[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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