Identification of a vitamin K‐dependent carboxylase in the venom duct of a Conus snail

Abstract
Peptides from the venom ducts of cone snails (genus Conus) contain γ‐carboxyglutamate residues. The γ‐glutamyl carboxylase responsible for this post‐translational modification is localized in the microsomal fraction, strictly dependent on vitamin K, activated by ammonium sulfate, and is associated with endogenous substrate. The K m of the enzyme for vitamin K is comparable to that for the bovine carboxylase. However, a propeptide containing substrate related to the blood coagulation protein factor IX, a highly efficient substrate for the bovine enzyme, was poorly carboxylated by the Conus enzyme, suggesting differences in γ‐carboxylase recognition signal sequences and/or structural requirements at the carboxylation site.