title: Mechanistic insights into cyclooxygenase irreversible inactivation by aspirin.
abstract: A mechanistic hypothesis for the acetylation of cyclooxygenase (COX) by aspirin is proposed on the basis of a QM/MM study. This mechanism is consistent with previous experimental findings by other investigators. Ser 530 appears to be acetylated under intramolecular general base catalysis provided by the carboxylate moiety of aspirin, while Tyr 385 plays a crucial role in orienting and polarizing the acetyl group.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy. paolo.tosco@unito.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Tosco
authors.forename: Loretta
authors.initials: L
authors.lastname: Lazzarato
mesh_terms: D000107:Acetylation; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001241:Aspirin / Q000737:chemistry*; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry*; D008956:Models, Chemical; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry* / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D012694:Serine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin