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How Mg2+ ions lower the SN2@P barrier in enzymatic triphosphate hydrolysis
Marc A van Bochove1, Goedele Roos, Célia Fonseca Guerra
1Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, Vrije Universiteit Amsterdam, De Boelelaan 1083, NL-1081 HV Amsterdam, The Netherlands. t.a.hamlin@vu.nl f.m.bickelhaupt@vu.nl.
Abstract:
Our quantum chemical activation strain analyses demonstrate how Mg2+ lowers the barrier of the enzymatic triphosphate hydrolysis through two distinct mechanisms: (a) weakening of the leaving-group bond, thereby decreasing activation strain; and (b) transition state (TS) stabilization through enhanced electrophilicity of the triphosphate PPP substrate, thereby strengthening the interaction with the nucleophile.
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