Free Radical Mechanism for the Y-Glutamyl Carboxylase Reaction : A Computational Study

Abstract

The purpose of this study was to discuss a combined energy profile for the radical mechanisms gamma-glutamyl carboxylase reaction. The initial step of the reaction mechanism involves a highly endothermic deprotonation of the naphthohydroquinone by the free amine. This reaction is found to be much less endothermic if a carboxylate anion is located close to the amine. The addition of the dioxygen molecule to the 4- position of the anion is thermodynamically preferred. The Dowd dioxetane occurs as a relatively low energy intermediate, but a hydroperoxyenolate anion is lower energy still. The dehydration of the quinone epoxide hydrate is only slightly exothermic, which may allow it to be reversible. Formation of the peroxyester dianion is a strongly endothermic reaction, and probably does not occur in the cell. Hydrogen atom transfer from tryptophan to either the Dowd dioxetane or the hydroperoxyenolate lowers the energy of the reaction by at least 0.045 a.u. (28 kcal mol–1)