Insights into the mechanism and inhibition of fatty acid amide hydrolase from quantum mechanics/molecular mechanics (QM/MM) modelling. (20th March 2009)

• Record Type: Journal Article
• Authors: Lodola, Alessio; Mor, Marco; Sirirak, Jitnapa; Mulholland, Adrian J.
• Is Part Of: Biochemical Society transactions. Volume 37:Number 2(2009)
• Page Start: 363
• Page End: 367
• Publication Date: 2009-03-20
• Subjects: fatty acid amide hydrolase (FAAH) -- inhibitor design -- quantum mechanics/molecular mechanics (QM/MM) -- reaction mechanism -- tetrahedral intermediate -- transition state; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0370363
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : FAAH (fatty acid amide hydrolase) is a promising target for the treatment of several central nervous system and peripheral disorders. Combined QM/MM (quantum mechanics/molecular mechanics) calculations have elucidated the role of its unusual catalytic triad in the hydrolysis of oleamide and oleoylmethyl ester substrates, and have identified the productive inhibitor-binding orientation for the carbamoylating compound URB524. These are potentially crucial insights for designing new covalent inhibitors of this drug target.