3mn8
Structure of Drosophila melanogaster carboxypeptidase D isoform 1B shortStructure of Drosophila melanogaster carboxypeptidase D isoform 1B short
Structural highlights
FunctionCBPD_DROME Metallocarboxypeptidase that catalyzes the release of C-terminal arginine or lysine residues from peptides and proteins (PubMed:12393882, PubMed:16556608, PubMed:20386952, PubMed:20600119, PubMed:31309630). Functionally important for processing a broad range of proteins including growth factors, peptide hormones (such as Akh) and neuropeptides (PubMed:16556608, PubMed:20386952, PubMed:20600119, PubMed:27430952, PubMed:31309630). Consequently, it is involved in a wide range of processes including viability, memory formation, locomotive activity, wing formation, and peptide-regulated behaviors such as starvation-induced hyperactivity, appetitive gustatory preference, and cold and ethanol sensitivity (PubMed:20386952, PubMed:20600119, PubMed:27430952, PubMed:31309630). Key enzyme in neuropeptide processing (PubMed:31309630). Involved in regulation of memory formation, possibly via the insulin pathway in neurosecretory cells (PubMed:27430952).[1] [2] [3] [4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDrosophila melanogaster silver gene is the ortholog of the coding gene of mammalian carboxypeptidase D (CPD). The silver gene gives rise to eight different splicing variants of differing length that can contain up to three homologous repeats. Among the protein variants encoded, the short form 1B alias DmCPD1Bs (D. melanogaster CPD variant 1B short) is necessary and sufficient for viability of the fruit fly. It has one single repeat, it is active against standard peptide substrates, and it is localized to the secretory pathway. In this work, the enzyme was found as a monomer in solution and as a homodimer in the crystal structure, which features a protomer with an N-terminal 311-residue catalytic domain of alpha/beta-hydrolase fold and a C-terminal 84-residue all-beta transthyretin-like domain. Overall, DmCPD1Bs conforms to the structure of N/E-type funnelins/M14B metallopeptidases, but it has two unique structural elements potentially involved in regulation of its activity: (i) two contiguous surface cysteines that may become palmitoylated and target the enzyme to membranes, thus providing control through localization, and (ii) a surface hot spot targetable by peptidases that would provide a regulatory mechanism through proteolytic inactivation. Given that the fruit fly possesses orthologs of only two out of the five proteolytically competent N/E-type funnelins found in higher vertebrates, DmCPD1Bs may represent a functional analog of at least one of the missing mammalian CPs. Structure-function analysis of the short splicing variant carboxypeptidase encoded by Drosophila melanogaster silver.,Tanco S, Arolas JL, Guevara T, Lorenzo J, Aviles FX, Gomis-Ruth FX J Mol Biol. 2010 Aug 20;401(3):465-77. Epub 2010 Jun 25. PMID:20600119[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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