title: Structural insight into the crucial role of ligand chirality in the activation of PPARs by crystallographic methods.
abstract: Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular disease, obesity, and diabetes. These receptors show a high degree of stereoselectivity towards several classes of drugs. This review provides an overview of most papers reporting the influence of stereochemistry on PPAR activation. Some cases in which chirality is a crucial point in determining the PPAR binding mode are reviewed and discussed with the aim to show how enantiomeric recognition originates at the molecular level. The structural characterization by crystallographic methods of complexes formed by PPARs with their ligands turns out to be an essential tool to explain receptor stereoselectivity.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari A. Moro, via Orabona 4, 70126 Bari, Italia. floiodice@farmchim.uniba.it
authors.forename: F
authors.initials: F
authors.lastname: Loiodice
authors.forename: G
authors.initials: G
authors.lastname: Pochetti
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D003460:Crystallization; D018360:Crystallography, X-Ray; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D058607:Fibric Acids / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D009928:Organ Specificity; D047492:Peroxisome Proliferator-Activated Receptors / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D058607:Fibric Acids; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D045162:Thiazolidinediones