Identification of a Drosophila vitamin K-dependent gamma-glutamyl carboxylase

Using reduced vitamin K, oxygen, and carbon dioxide, gamma-glutamyl carboxy lase post-translationally modifies certain glutamates by adding carbon diox ide to the gamma position of those amino acids. In vertebrates, the modific ation of glutamate residues of target proteins is facilitated by an interac tion between a propeptide present on target proteins and the gamma-glutamyl carboxylase, Previously, the gastropod Conus was the only known invertebra te with a demonstrated vitamin K-dependent carboxylase. We report here the discovery of a gamma-glutamyl carboxylase in Drosophila, This Drosophila en zyme is remarkably similar in amino acid sequence to the known mammalian ca rboxylases; it has 33% sequence identity and 45% sequence similarity to hum an gamma-glutamyl carboxylase, The Drosophila carboxylase is vitamin K-depe ndent, and it has a K-m toward a model pentapeptide substrate, FLEEL, of ab out 4 mM. However, unlike the human gamma-glutamyl carboxylase, it is not s timulated by human blood coagulation factor IX propeptides. We found the mR NA for Drosophila gamma-glutamyl carboxylase in virtually every embryonic a nd adult stage that we investigated, with the highest concentration evident in the adult head.