Density functional theory investigation of guanosine triphosphate models. Catalytic role of Mg2 ions in phosphate ester hydrolysis

Hydrolysis of phosphate ester bonds is a key reaction in biological systems and many enzymes require one or more metal ions as cofactors to catalyse this reaction. However, the exact role of metal ions is still unclear. In this contribution, we have investigated the influence of Mg2 on the hydrolysis of guanosine triphosphate (GTP) models using Density Functional Theory (DFT). Results indicate that Mg2 catalyses phosphate ester hydrolysis, stabilizing the transition state (TS) both for associative and dissociative pathways. In the associative pathway, the reaction is promoted by an increased electrophilicity of the reactive phosphor-us atom, whereas in the dissociative pathway catalysis is achieved by stabilization of beta-phosphate due to Mg2 coordination. Considering relative energy values, it turns out that the dissociative pathway is more favorable. (C) 2003 Elsevier Science B.V. All rights reserved