Quantum Chemical Study of the Mechanism of Action of Vitamin K Carboxylase in Solvent.

We investigate the post-translational generation of Gla (γ-carboxy glutamic acid) from Glu (glutamic acid) by vitamin K carboxylase (VKC) in solvent. VKC is thought to convert vitamin K, in the vitamin K cycle, to an alkoxide-epoxide form, which then reacts with CO(2) to generate an essential ingredient in blood coagulation, γ-carboxyglutamic acid (Gla). The generation of Gla from Glu is found to be exergenic (-15 kcal/mol) in aqueous solution with the SM6 method. We also produced the free energy profile for this model biochemical process with other solvent methods (polarizable continuum model, dielectric polarizable continuum model) and different dielectric constants. The biological implications are discussed.