title: A proposed molecular basis for the selective resveratrol inhibition of the PGHS-1 peroxidase activity.
abstract: Docking results have enabled us to propose how resveratrol could act as a selective PGHS-1 peroxidase site inhibitor. The docking model has predicted a slightly less favorable DeltaG(bind) (-17.9 kcal/mol) of the resveratrol to the PGHS-2 peroxidase site in comparison with its corresponding binding to the PGHS-1 (-20.4 kcal/mol). The formation of hydrogen bonds among the hydroxyl groups of the resveratrol phenyl rings, the backbone of Fe-heme and the carbonyl group of Leu294 inside the PGHS-1 peroxidase site, associated with the absence of His214 in the backbone of PGHS-1, are essential features that are required to maintain the aromatic rings of the natural product parallel to the Fe-heme group and transverse to the peroxidase access channel promoting a large steric hindrance at this site and its consequent selective inhibition.
authors.affiliation: Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, PO Box 68023, RJ 21944-971, Brazil.
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Kümmerle
authors.forename: Gilberto M
authors.initials: GM
authors.lastname: Sperandio da Silva
authors.forename: Carlos M R
authors.initials: CM
authors.lastname: Sant'Anna
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
mesh_terms: D001665:Binding Sites; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D010544:Peroxidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D016861:Cyclooxygenase Inhibitors; D013267:Stilbenes; D010544:Peroxidases; D051545:Cyclooxygenase 1; D000077185:Resveratrol