3MN8

Structure of Drosophila melanogaster carboxypeptidase D isoform 1B short

Summary for 3MN8

• Entry DOI: 10.2210/pdb3mn8/pdb
• Related: 1H8L 1QMU
• Descriptor: LP15968p, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total)
• Functional Keywords: catalytic domain of alpha/beta-hydrolase fold, c-terminal, all-beta transthyretin-like domain, hydrolase
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 4
• Total formula weight: 196897.39

Authors

Tanco, S.,Arolas, J.L.,Guevara, T.,Lorenzo, J.,Aviles, F.X.,Gomis-Ruth, F.X. (deposition date: 2010-04-21, release date: 2010-07-28, Last modification date: 2024-11-20)

Primary citation

Tanco, S.,Arolas, J.L.,Guevara, T.,Lorenzo, J.,Aviles, F.X.,Gomis-Ruth, F.X.
Structure-Function Analysis of the Short Splicing Variant Carboxypeptidase Encoded by Drosophila melanogaster silver.
J.Mol.Biol., 401:465-477, 2010

PubMed Abstract: Drosophila 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.

PubMed: 20600119
DOI: 10.1016/j.jmb.2010.06.035

Experimental method

X-RAY DIFFRACTION (2.7 Å)