Fluvastatin reduces endothelial tissue factor expression: effect on NF-kB translocation

The vitamin K-dependent γ-glutamyl carboxylase catalyzes the conversion of glutamic acid to γ-carboxyglutamic acid in substrate proteins. The enzyme has recently been purified and the cDNA encoding the enzyme has been cloned. The availability of recombinant enzyme provides the opportunity to probe the mechanism of this unique enzyme. The binding sites for the γ-carboxylation recognition site containing propeptide and carboxylatable glutamate residues of a vitamin K-dependent substrate protein have been localized to the amino-terminal 250 residues of the enzyme. Regions of the carboxy-terminal of the enzyme are important for conversion of vitamin K hydroquinone to vitamin K epoxide, a reaction that occurs concomitantly with carboxylation and is catalyzed by the vitamin K-dependent carboxylase. Using pure recombinant vitamin K-dependent carboxylase it has been demonstrated that catalysis of vitamin K oxygenation by the enzyme is regulated by the availability of carboxylatable substrate.