title: Identification of a Drosophila vitamin K-dependent gamma-glutamyl carboxylase.
abstract: Using reduced vitamin K, oxygen, and carbon dioxide, gamma-glutamyl carboxylase post-translationally modifies certain glutamates by adding carbon dioxide to the gamma position of those amino acids. In vertebrates, the modification of glutamate residues of target proteins is facilitated by an interaction between a propeptide present on target proteins and the gamma-glutamyl carboxylase. Previously, the gastropod Conus was the only known invertebrate with a demonstrated vitamin K-dependent carboxylase. We report here the discovery of a gamma-glutamyl carboxylase in Drosophila. This Drosophila enzyme is remarkably similar in amino acid sequence to the known mammalian carboxylases; it has 33% sequence identity and 45% sequence similarity to human gamma-glutamyl carboxylase. The Drosophila carboxylase is vitamin K-dependent, and it has a K(m) toward a model pentapeptide substrate, FLEEL, of about 4 mm. However, unlike the human gamma-glutamyl carboxylase, it is not stimulated by human blood coagulation factor IX propeptides. We found the mRNA for Drosophila gamma-glutamyl carboxylase in virtually every embryonic and adult stage that we investigated, with the highest concentration evident in the adult head.
authors.affiliation: Department of Biology, Center for Thrombosis and Homeostasis, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.forename: C T
authors.initials: CT
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Jin
authors.forename: D W
authors.initials: DW
authors.lastname: Stafford
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019735:Carbon-Carbon Ligases / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013379:Substrate Specificity; D014812:Vitamin K / Q000378:metabolism*
chemical_list: D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase