The unique and characteristic feature of vitamin K-dependent proteins is the presence of gamma-carboxyglutamyl (Gla) residues formed during the posttranslational processing of these proteins. The energy needed to drive this microsomal carboxylation event comes from the reoxidation of the reduced, hydronaphthoquinone form of vitamin K to its 2,3-epoxide. Recent studies have suggested that an intermediate epoxide alkoxide is the strong base needed to abstract a proton from the relatively unreactive methylene carbon of the glutamyl residue. The primary gene product of the vitamin K-dependent proteins contains a homologous propeptide extension between the amino terminus of the mature protein and signal peptide. This region, which is cleaved before secretion of these proteins, serves to dock the protein substrate to the enzyme catalyzing the carboxylation event, and to also alter the apparent Km of the Glu binding site of the enzyme. The order in which the multiple Glu sites on the substrate proteins are carboxylated is unknown, but elucidation of this property of the enzyme and further details of the bioorganic mechanism should be aided by recent reports of purification of this unique carboxylase.