Dineopentyl phosphate hydrolysis: evidence for stepwise water attack

The Journal of Organic Chemistry
S C L KamerlinArieh Warshel

Abstract

Phosphate ester hydrolysis is ubiquitous in biology, playing a central role in energy production, signaling, biosynthesis, and the regulation of protein function among other things. Although the mechanism of action of the enzymes regulating this reaction has been the focus of intensive research in the past few decades, the correct description of this apparently simple reaction remains controversial. A clear understanding of the mechanism that takes place in solution is crucial to be able to evaluate whether proposals for the enzyme-catalyzed mechanisms are reasonable. For the pH-independent hydrolysis of phosphate diesters, several kinetically equivalent mechanisms are plausible, including hydroxide attack on the neutral phosphate. However, it is very difficult to measure the rate of this reaction directly by experimental methods, so it has been evaluated by examining the rate of hydrolysis of neutral phosphate triesters, where a methyl group has replaced a proton. This may not be an accurate model of the neutral phosphate diester and does not provide information about a reaction pathway that is concerted with nucleophilic attack to generate a similar phosphorane. We have carefully mapped out free energy surfaces for both hydro...Continue Reading

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Citations

Jan 16, 2013·Quarterly Reviews of Biophysics·Shina C L KamerlinArieh Warshel
Apr 4, 2012·Journal of the American Chemical Society·Rachel GlavesDominik Marx
Jul 31, 2010·Physical Chemistry Chemical Physics : PCCP·Brigitta Elsässer, Gregor Fels
May 8, 2010·Chemical Communications : Chem Comm·Randy B Stockbridge, Richard Wolfenden
Jun 4, 2013·Physical Chemistry Chemical Physics : PCCP·Fernanda DuarteShina Caroline Lynn Kamerlin
Nov 26, 2014·Journal of the American Chemical Society·Fernanda DuarteShina C L Kamerlin
May 30, 2009·Proteins·Alexandra Vardi Kilshtain, Arieh Warshel
Jul 6, 2010·Proteins·Enrique MarcosRamon Crehuet
Aug 26, 2015·Organic & Biomolecular Chemistry·I BordesV Moliner
Sep 25, 2014·Journal of Computational Chemistry·Shinichi YamabeShigeyoshi Sakaki
Jun 10, 2011·Organic & Biomolecular Chemistry·Shina C L Kamerlin, John Wilkie
May 1, 2012·Chemical Communications : Chem Comm·Fabrizio MancinPaolo Tecilla
May 3, 2018·Beilstein Journal of Organic Chemistry·Satu MikkolaHarri Lönnberg
Mar 21, 2009·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Shina C L KamerlinArieh Warshel
Dec 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jinping LeiXuhui Huang
Nov 6, 2009·The Journal of Physical Chemistry. B·Shina C L Kamerlin, Arieh Warshel
Oct 13, 2009·The Journal of Physical Chemistry. B·Dalva E C FerreiraFaruk Nome
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhangxia Wang, Haibo Ma
Oct 19, 2017·The Journal of Physical Chemistry. a·Carles Acosta-SilvaAntoni Oliva
Oct 26, 2021·Journal of Agricultural and Food Chemistry·Eric M BrownNed B Bowden

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