9l3t

PPARgamma Ligand binding domain in complex with piperine

spinqualitylabelsall models 9l3t, resolution 2.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9l3t is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.36Å Ligands: AYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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. 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. Publication Abstract from PubMed Piperine has been investigated for a diverse array of biological effects, including a potential role in modulating peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that plays a pivotal role in regulating lipid and glucose metabolism. This study conducted a comprehensive co-crystallographic analysis of the complex of piperine with the PPARgamma ligand-binding domain (PPARgamma-LBD), with the objective of elucidating the precise binding interactions of piperine. The co-crystal structure revealed that piperine binds within the ligand-binding pocket of PPARgamma-LBD via hydrogen-bonding and hydrophobic interactions with residues of the ligand-binding site. Notably, in contrast to conventional full agonists, piperine does not directly stabilize helix H12. This could contribute to the comparatively weaker agonistic activity of piperine. The results of this study also suggest that piperine binding facilitates a role as a partial agonist or even an antagonist under certain physiological conditions. Collectively, these findings contribute to a greater understanding of the manner in which piperine modulates PPARgamma function and its potential as a therapeutic candidate for the treatment of metabolic disorders. Given its natural origin and relatively minimal side-effect profile, piperine and its derivatives could be promising alternatives to synthetic PPARgamma modulators such as thiazolidinediones, which have significant side effects. Molecular interactions between piperine and peroxisome proliferator-activated receptor gamma ligand-binding domain revealed using co-crystallization studies.,Egawa D, Ishida H, Katakawa K Acta Crystallogr F Struct Biol Commun. 2025 May 1. doi: , 10.1107/S2053230X25002377. PMID:40172924 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA