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M18 peptidase aspartyl aminopeptidase Peptidase M18 family, aspartyl aminopeptidase (DAP; EC 3.4.11.21) subfamily, is widely distributed in bacteria and eukaryotes. DAP cleaves only unblocked N-terminal acidic amino-acid residues. It is a cytosolic enzyme and is highly conserved; for example, the human enzyme has 51% identity to an aspartyl aminopeptidase-like protein in Arabidopsis thaliana. The mammalian DAP is highly selective for hydrolysis of N-terminal aspartate or glutamate residues from peptides. Unlike glutamyl aminopeptidase (M42), DAP does not cleave simple aminoaryl-arylamide substrates. Although there is lack of understanding of the function of this enzyme, it is thought to act in concert with other aminopeptidases to facilitate protein turnover because of their restricted specificities for the N-terminal aspartic and glutamic acid, which cannot be cleaved by any other aminopeptidases. The mammalian aspartyl aminopeptidase is possibly contributing to the catabolism of peptides, including those produced by the proteasome. It may also trim the N-terminus of peptides that are intended for the MHC class I system. In humans, DAP has been implicated in the specific function of converting angiotensin II to the vasoactive angiotensin III within the brain. Saccharomyces cerevisiae aminopeptidase I (Ape1) is involved in protein degradation in vacuoles (the yeast lysosomes) where it is transported by the unique cytoplasm-to-vacuole targeting (Cvt) pathway under vegetative growth conditions and by the autophagy pathway during starvation. Its N-terminal propeptide region, which mediates higher-order complex formation, serves as a scaffolding cargo critical for the assembly of the Cvt vesicle for vacuolar delivery. Pseudomonas aeruginosa aminopeptidase (PaAP) shows that its activity is dependent on Co2+ rather than Zn2+, and is thus a cocatalytic cobalt peptidase rather than a zinc-dependent peptidase. |
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