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PDBsum entry 3mn8
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References listed in PDB file
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Key reference
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Title
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Structure-Function analysis of the short splicing variant carboxypeptidase encoded by drosophila melanogaster silver.
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Authors
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S.Tanco,
J.L.Arolas,
T.Guevara,
J.Lorenzo,
F.X.Avilés,
F.X.Gomis-Rüth.
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Ref.
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J Mol Biol, 2010,
401,
465-477.
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PubMed id
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Abstract
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Drosophila melanogaster silver gene is the ortholog of the coding gene of
mammalian carboxypeptidase D. 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 is
necessary and sufficient for viability of the fruitfly. 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 solution and 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
hotspot targetable by peptidases that would provide a regulatory mechanism
through proteolytic inactivation. Given that the fruitfly 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 carboxypeptidases.
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