Structure–Function Analysis of the Short Splicing Variant Carboxypeptidase Encoded by Drosophila melanogaster silver

摘要: Drosophila melanogaster silver gene is the ortholog of coding mammalian carboxypeptidase D (CPD). The gives rise to eight different splicing variants differing length that can contain up three homologous repeats. Among protein encoded, short form 1B alias DmCPD1Bs (D. CPD variant short) necessary and sufficient for viability fruit fly. It has one single repeat, it active against standard peptide substrates, localized secretory pathway. In this work, enzyme was found as a monomer in solution homodimer crystal structure, which features protomer with an N-terminal 311-residue catalytic domain α/β-hydrolase fold C-terminal 84-residue all-β transthyretin-like domain. Overall, conforms structure N/E-type funnelins/M14B metallopeptidases, but two unique structural elements potentially involved regulation its activity: (i) contiguous surface cysteines may become palmitoylated target membranes, thus providing control through localization, (ii) hot spot targetable by peptidases would provide regulatory mechanism proteolytic inactivation. Given fly possesses orthologs only out five proteolytically competent funnelins higher vertebrates, represent functional analog at least missing CPs.