Catalytic mechanism and energy barriers for butyrylcholinesterase-catalyzed hydrolysis of cocaine.

ABSTRACT: The geometries of the transition states, intermediates, and prereactive enzyme-substrate complex and the corresponding energy barriers have been determined by performing hybrid quantum mechanical/molecular mechanical (QM/MM) calculations on butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)- and (+)-cocaine. The energy barriers were evaluated by performing QM/MM calculations with the QM method at the MP2/6-31+G* level and the MM method using the AMBER force field. These calculations allow us to account for the protein environmental effects on the transition states and energy barriers of these enzymatic reactions, showing remarkable effects of the protein environment on intermolecular hydrogen bonding (with an oxyanion hole), which is crucial for the transition state stabilization and

SUBMITTER: Zhan CG 

PROVIDER: S-EPMC1366953 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature