title: QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation.
abstract: Fatty acid amide hydrolase (FAAH), a promising target for the treatment of several central and peripheral nervous system disorders, such as anxiety, pain and hypertension, has an unusual catalytic site, and its mechanism has been uncertain; hybrid quantum mechanics/molecular mechanics (QM/MM) calculations reveal a new mechanism of nucleophile activation (involving a Lys-Ser-Ser catalytic triad), with potentially crucial insights for the design of potent and selective inhibitors.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma, 43100, Parma, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Lodola
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Hermann
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases