| Family type peptidase | M18.001 - aminopeptidase I (Saccharomyces cerevisiae), MEROPS Accession MER0001255 (peptidase unit: 46-514) |
| Content of family | Peptidase family M18 contains metalloaminopeptidases. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
Family M18 is widely distributed in bacteria and eukaryotes, but only two peptidases in the family have yet been characterised in any detail: yeast aminopeptidase I (M18.001) and mammalian aspartyl aminopeptidase (M18.002). |
| Catalytic type | Metallo |
| Active site residues | H132 D134 D303 E339 E340 D385 H479 |
| Active site | Active site residues have not been identified with certainty, but for aspartyl aminopeptidase (M18.002), mutation of three His residues abolished enzymatic activity (Wilk et al., 2002). The first and third of these residues correspond with the first (H132) and last (H479) of the seven active site residues proposed for the family by MEROPS (see above). The other residues proposed by MEROPS (D134, D303, E339, E340, D385, H479) are well conserved in the alignment for the family, and agree with those in the families of clan MH (M20, M28, M42). |
| Activities and specificities | Yeast aminopeptidase I is active only in its dodecameric form (see below). It has broad substrate specificity, acting on N-terminal leucine and most other amino acids, but acts only slowly on Leu NHPhNO2 (Metz & Rohm, 1976). In contrast, the mammalian aspartyl aminopeptidase is highly selective for hydrolysis of N-terminal Asp or Glu residues from peptides, and does not accept the arylamide leaving groups that are used in test substrates for many other aminopeptidases (Wilk et al., 1998). A coupled assay with AspAla-Pro-NHNap was used in which dipeptidyl-peptidase IV (S09.003) completed the liberation of the detectable 2-naphthylamine. |
| Molecular structure | The mature yeast aminopeptidase I is a non-disulfide-linked dodecamer, in which each monomer contains two zinc ions (Metz & Rohm, 1976; Metz et al., 1977). It is notable that the bacterial aminopeptidase, M42.003, also in clan MH, similarly exists as a homo-dodecameric complex (Russo & Baumann, 2004).
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| Clan | MH |
| Basis of clan assignment | For members of this family and family M28 predicted metal ligands occur in the same order in the sequence: H, D, E, D/E, H; and active site residues in the motifs HXD and EE |
