Semiempirical molecular orbital studies of the acylation step in the lipase-catalyzed ester hydrolysis

In this study, we present the results from the semiempirical molecular orbital calculations for the acylation step in the lipase-catalyzed ester hydrolysis. The results reveal that the lowest energy path for the formation of the tetrahedral intermediate is for the serine residue of the catalytic triad to attack the substrate, followed by coupling heavy atom movement and proton transfer. The calculations of four active site models show that the cooperation of the aspartate group and the oxyanion hole is capable of lowering the activation energy by about 16 kcalmol^-1. Our results further suggest that the lipase-catalyzed ester hydrolysis adopts the single proton transfer mechanism.