Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and signaling pathways throughout all kingdoms of life. This hierarchy contains zinc peptidases that correspond to the MH clan in the MEROPS database, which contains 4 families (M18, M20, M28, M42). The peptidase M20 family includes carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase. The dipeptidases include bacterial dipeptidase, peptidase V (PepV), a non-specific eukaryotic dipeptidase, and two Xaa-His dipeptidases (carnosinases). There is also the bacterial aminopeptidase, peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. Peptidase family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. However, several enzymes in this family utilize other first row transition metal ions such as cobalt and manganese. Each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Glutamate carboxypeptidase II and plasma glutamate carboxypeptidase hydrolyze dipeptides. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 is widely distributed in bacteria and eukaryotes. However, only yeast aminopeptidase I and mammalian aspartyl aminopeptidase have been characterized in detail. Some M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacyl-peptidase activity (i.e. hydrolysis of acylated N-terminal residues).

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gi 609252570  10 YGSKYKPkTHTIVLNSGAVLSVNAKGR 36
Cdd:cd05658  331 YPEKHEP-NHRPVLNKGPVIKVNANQR 356

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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gi 609252570  10 YGSKYKPkTHTIVLNSGAVLSVNAKGR 36
Cdd:cd05658  331 YPEKHEP-NHRPVLNKGPVIKVNANQR 356

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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gi 609252570  10 YGSKYKPkTHTIVLNSGAVLSVNAKGR 36
Cdd:cd05658  331 YPEKHEP-NHRPVLNKGPVIKVNANQR 356