The effect of magnesium ions on triphosphate hydrolysis

• Published in: Pure and applied chemistry Vol. 89; no. 6; pp. 715 - 727
• Main Authors: Barrozo, Alexandre, Blaha-Nelson, David, Williams, Nicholas H., Kamerlin, Shina C. L.
• Format: Journal Article
• Language: English
• Published: Berlin De Gruyter 27.06.2017; Walter de Gruyter GmbH
• Subjects: acetyl phosphate; Aqueous solutions; Density functional theory; density functional theory (DFT); Hydrolysis; ICPOC-23; Magnesium; Metal ions; metals in biology; methyl triphosphate; Phosphate esters; phosphate hydrolysis; Solvents; Substrates
• ISSN: 0033-4545; 1365-3075; 1365-3075
• DOI: 10.1515/pac-2016-1125

The role of metal ions in catalyzing phosphate ester hydrolysis has been the subject of much debate, both in terms of whether they change the transition state structure or mechanistic pathway. Understanding the impact of metal ions on these biologically critical reactions is central to improving our understanding of the role of metal ions in the numerous enzymes that facilitate them. In the present study, we have performed density functional theory studies of the mechanisms of methyl triphosphate and acetyl phosphate hydrolysis in aqueous solution to explore the competition between solvent- and substrate-assisted pathways, and examined the impact of Mg on the energetics and transition state geometries. In both cases, we observe a clear preference for a more dissociative solvent-assisted transition state, which is not significantly changed by coordination of Mg . The effect of Mg on the transition state geometries for the two pathways is minimal. While our calculations cannot rule out a substrate-assisted pathway as a possible solution for biological phosphate hydrolysis, they demonstrate that a significantly higher energy barrier needs to be overcome in the enzymatic reaction for this to be an energetically viable reaction pathway.