title: Conformational effects in enzyme catalysis: reaction via a high energy conformation in fatty acid amide hydrolase.
abstract: Quantum mechanics/molecular mechanics and molecular dynamics simulations of fatty acid amide hydrolase show that reaction (amide hydrolysis) occurs via a distinct, high energy conformation. This unusual finding has important implications for fatty acid amide hydrolase, a key enzyme in the endocannabinoid system. These results demonstrate the importance of structural fluctuations and the need to include them in the modeling of enzyme reactions. They also show that approaches based simply on studying enzyme-substrate complexes can be misleading for understanding biochemical reactivity.
authors.forename: Alessio
authors.initials: A
authors.lastname: Lodola
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.forename: Jolanta
authors.initials: J
authors.lastname: Zurek
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Harvey
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D003198:Computer Simulation; D004735:Energy Transfer; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000099252:Fatty Acid Amide Hydrolases