title: Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study.
abstract: In the reaction cycle of glutamate carboxylase, vitamin K epoxidation by O2 has been proposed to generate a very strong base able to remove a proton from the gamma carbon of a Glu residue, thus yielding a Glu-based carbanion that readily reacts with CO2. We have used hybrid density functional theory to study this appealing mechanism. Our calculations show a very exergonic four-step mechanism with the reaction of (triplet) O2 with the singlet vitamin K anion as the rate-limiting step, with a rate similar to the experimental value. Our study also establishes the need to apply continuum models when performing the optimization of minimum-energy crossing points between potential energy surfaces of different multiplicities for enzyme model systems.
authors.affiliation: REQUIMTE, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150 Porto-Portugal.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Silva
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Ramos
mesh_terms: D000838:Anions / Q000737:chemistry; D019735:Carbon-Carbon Ligases / Q000737:chemistry*; D003198:Computer Simulation; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry
chemical_list: D000838:Anions; D018698:Glutamic Acid; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D010100:Oxygen