Aspects of the mechanism of catalysis in phospholipase A2•A combined ab initio molecular orbital and molecular mechanics study

A combination of ab initio molecular orbital and molecular mechanics calculations has been used to estimate the energetics of the formation of the tetrahedral intermediate involved in the catalytic ester hydrolysis by the enzyme PLA2. A number of models have been studied which differ in the extent to which the environment of the enzyme is included. The calculations provide support for the mechanism of catalysis involving nucleophilic attack of water activated by proton transfer to His-48. A single, rather than a double, proton-transfer mechanism, involving His-48, is favoured.