title: Biochemical characterization of Drosophila gamma-glutamyl carboxylase and its role in fly development.
abstract: To investigate structure-function relationships in gamma-glutamyl carboxylases, the enzyme from Drosophila melanogaster was characterized. Four cysteine residues were shown to be important determinants for enzymatic activity. Native Drosophila substrates have not yet been identified, but propeptides of human prothrombin and factor IX are recognized by the Drosophila enzyme. The presence of the propeptide region increased apparent affinity by approximately 200-fold, and mutation of a hydrophobic residue of factor IX propeptide (F-16A) decreased carboxylation by 90%, as in the human enzyme. Substrate recognition appears to be highly conserved between the human and Drosophila gamma-glutamyl carboxylases. Inactivation of Drosophila gamma-glutamyl carboxylase by non-sense mutations or insertional mutagenesis by P-element insertion have no apparent effects on growth and fertility under laboratory conditions.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, 84112, USA. bandyop@biology.utah.edu
authors.forename: P K
authors.initials: PK
authors.lastname: Bandyopadhyay
authors.forename: K
authors.initials: K
authors.lastname: Clark
authors.forename: B J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
authors.forename: K G
authors.initials: KG
authors.lastname: Golic
authors.forename: Y S
authors.initials: YS
authors.lastname: Rong
mesh_terms: D000409:Alanine / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D019735:Carbon-Carbon Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003545:Cysteine / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology* / Q000254:growth & development; D005298:Fertility; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000378:metabolism; D014812:Vitamin K / Q000502:physiology
chemical_list: D010455:Peptides; D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D003545:Cysteine; D000409:Alanine