QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation.
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.
Lodola
Alessio
A
Dipartimento Farmaceutico, Università degli Studi di Parma, 43100, Parma, Italy.
Mor
Marco
M
Hermann
Johannes C
JC
Tarzia
Giorgio
G
Piomelli
Daniele
D
Mulholland
Adrian J
AJ
D000581:Amidohydrolases / Q000737:chemistry*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases