3vji
From Proteopedia
Human PPAR gamma ligand binding domain in complex with JKPL53
Structural highlights
Disease[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: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. Function[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.[4] [5] [6] Publication Abstract from PubMedHuman peroxisome proliferator-activated receptors (hPPARs) are ligand-dependent transcription factors that control various biological responses, and there are three subtypes: hPPARalpha, hPPARdelta, and hPPARgamma. We report here that alpha-substituted phenylpropanoic acid-type hPPAR agonists with similar structure bind to the hPPAR ligand binding domain (LBD) in different conformations, depending on the receptor subtype. These results might indicate that hPPAR ligand binding pockets have multiple binding points that can be utilized to accommodate structurally flexible hPPAR ligands. Peroxisome proliferator-activated receptors (PPARs) have multiple binding points that accommodate ligands in various conformations: phenylpropanoic acid-type PPAR ligands bind to PPAR in different conformations, depending on the subtype.,Kuwabara N, Oyama T, Tomioka D, Ohashi M, Yanagisawa J, Shimizu T, Miyachi H J Med Chem. 2012 Jan 26;55(2):893-902. Epub 2012 Jan 10. PMID:22185225[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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