A theoretical study of hydrolysis by phospholipase A2: the catalytic role of the active site and substrate specificity

Abstract

A computational model, which involves the combination of molecular mechanics and molecular-orbital methods, has been developed to study the energetics of phospholipid hydrolysis in the active site of phospholipase A₂. This model has been found to explain the catalytic role of the active site and is able to quantify differences in binding and hydrolysis between an ester and amide substrate. The mechanism of catalysis proposed on the basis of structural data is shown to be in accord with currently available experimental data.