Williams, N.H., Baarrozo, A., Blaha-Nelson, D. et al. (1 more author) (2017) The effect of magnesium ions on triphosphate hydrolysis. Pure and Applied Chemistry. ISSN 0033-4545
Abstract
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 Mg2+ 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 Mg2+. The effect of Mg2+ 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 De Gruyter. This is an author produced version of a paper subsequently published in Pure and Applied Chemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | acetyl phosphate; density functional theory (DFT); ICPOC-23; metals in biology; methyl triphosphate; phosphate hydrolysis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Mar 2017 11:01 |
Last Modified: | 26 Feb 2018 01:38 |
Published Version: | https://doi.org/10.1515/pac-2016-1125 |
Status: | Published |
Publisher: | De Gruyter |
Refereed: | Yes |
Identification Number: | 10.1515/pac-2016-1125 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112938 |