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: Alessio Lodola, Marco Mor, Johannes C Hermann, Giorgio Tarzia, Daniele Piomelli, Adrian J Mulholland
• Journal: Chemical communications (Cambridge, England) (Chem Commun (Camb)) Issue 35 Pg. 4399-401 (Sep 21 2005) ISSN: 1359-7345 [Print] England
• PMID: 16136230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Amidohydrolases
• fatty-acid amide hydrolase

Topics

• Amidohydrolases (chemistry)
• Catalysis
• Enzyme Inhibitors (chemistry)
• Kinetics
• Models, Molecular