Do electrostatic interactions with positively charged active site groups tighten the transition state for enzymatic phosphoryl transfer?

Journal of the American Chemical Society
Ivana Nikolic-HughesDaniel Herschlag

Abstract

The effect of electrostatic interactions on the transition-state character for enzymatic phosphoryl transfer has been a subject of much debate. In this work, we investigate the transition state for alkaline phosphatase (AP) using linear free-energy relationships (LFERs). We determined k(cat)/K(M) for a series of aryl sulfate ester monoanions to obtain the Brønsted coefficient, beta(lg), and compared the value to that obtained previously for a series of aryl phosphorothioate ester dianion substrates. Despite the difference in substrate charge, the observed Brønsted coefficients for AP-catalyzed aryl sulfate and aryl phosphorothioate hydrolysis (-0.76 +/- 0.14 and -0.77 +/- 0.10, respectively) are strikingly similar, with steric effects being responsible for the uncertainties in these values. Aryl sulfates and aryl phosphates react via similar loose transition states in solution. These observations suggest an apparent equivalency of the transition states for phosphorothioate and sulfate hydrolysis reactions at the AP active site and, thus, negligible effects of active site electrostatic interactions on charge distribution in the transition state.

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Citations

Jan 16, 2013·Quarterly Reviews of Biophysics·Shina C L KamerlinArieh Warshel
Jan 26, 2006·Journal of the American Chemical Society·Jesse G Zalatan, Daniel Herschlag
May 26, 2011·Journal of the American Chemical Society·Violeta López-CanutIñaki Tuñón
Dec 4, 2012·The Journal of Physical Chemistry. B·B Ram PrasadArieh Warshel
Jun 4, 2013·Physical Chemistry Chemical Physics : PCCP·Fernanda DuarteShina Caroline Lynn Kamerlin
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jagadeeswaran Chandrasekar, Scott K Silverman
Dec 7, 2011·Scientia pharmaceutica·Attila AlmásiPál Perjési
Apr 26, 2011·Annual Review of Biochemistry·Jonathan K LassilaDaniel Herschlag
Apr 7, 2007·Journal of the American Chemical Society·Irina CatrinaDaniel Herschlag
Jul 17, 2007·Journal of the American Chemical Society·Jesse G ZalatanAlvan C Hengge
Dec 31, 2015·Current Opinion in Structural Biology·Anna Pabis, Shina Caroline Lynn Kamerlin
Jul 18, 2006·Journal of Biochemical and Biophysical Methods·Attila AlmásiPál Perjési
Aug 14, 2012·Biochimica Et Biophysica Acta·Mark F Mohamed, Florian Hollfelder
May 18, 2016·Biochemistry·Anna PabisShina C L Kamerlin
Apr 1, 2014·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Shi-Lu Chen, Rong-Zhen Liao
Jun 22, 2007·Organic & Biomolecular Chemistry·Shina C L Kamerlin, John Wilkie
Jul 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Charlotte M MitonFlorian Hollfelder
Nov 23, 2007·ACS Chemical Biology·Jemy A GutierrezVern L Schramm
May 12, 2009·The Journal of Physical Chemistry. B·Violeta López-CanutIñaki Tuñón
Jun 21, 2015·Journal of the American Chemical Society·Alexandre BarrozoShina C L Kamerlin
May 4, 2006·Journal of the American Chemical Society·Paul G Loncke, Paul J Berti
Jun 30, 2005·Journal of the American Chemical Society·Ivana Nikolic-HughesDaniel Herschlag

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