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.