| Clan type peptidase | M28.002 - aminopeptidase Ap1 (Vibrio proteolyticus), MEROPS Accession MER0001284 (peptidase unit: 148-401); PDB accession 1AMP |
| History | Handbook of Proteolytic Enzymes, Academic Press, London (1998) |
| Description | Water nucleophile; water bound by two zinc ions ligated by His (or Asp), Asp, Glu, Asp (or Glu), His |
| Contents of clan | The clan contains a variety of zinc-dependent exopeptidases. |
| Evidence | The structures available for peptidases in families M20, M28 and M42 show similar proteins folds (see below), although it has been pointed out that different folding pathways must exist for some members of the clan (Murzin, 1998). Family M18 is included in the clan, in the absence of a structure, on the basis of conservation of probable active site residues that match those in the other families (see the Alignment for the clan). |
| Catalytic mechanism | The peptidases in clan MH are cocatalytic zinc peptidases containing two atoms of zinc per molecule, which have five amino acid ligands. The catalytic mechanism has been discussed in detail by Auld (2004) (see also Schurer et al., 2004). |
| Peptidase activity | All known cocatalytic metallopeptidases are exopeptidases. Clan MH contains aminopeptidases, carboxypeptidases, dipeptidases and tripeptidases. |
| Protein fold | The two metal ions are bound by five residues, which occur in the sequence in the order His, Asp, Glu, Asp or Glu, His; the first Asp binds both metal ions. An additional Asp and a Glu residue are thought to be important for catalysis and occur adjacent to metal ligands in the motifs HXD and EE. Tertiary structures have been determined for members of families M20 (Tucker et al., 1996), M28 (Chevrier et al., 1994) and M42 (Russo & Baumann, 2004). Peptidases in clan MH are alpha/beta proteins with a five-stranded beta sheet (in the order 21354, with strand 4 antiparallel to the rest) sandwiched between two layers of helices. The active site is at one end of the beta sheet. The fifth zinc ligand is on a loop at the C-terminus of variable length and can be difficult to predict in some members of the clan. The fold is similar to that of clans MC and ML, but because the metal ligands are not in equivalent positions we assume that the similarity is a result of parallel rather than divergent evolution; however, all three clans are included in the same SCOP superfamily (see SCOP sunid 53187). |
| Homologous non-peptidase families | There are several members of families in the clan that are not known to be peptidases, for example the transferrin receptor (M28.972) and aminoacylase (M20.973). N-acetylmuramoyl-L-alanine amidase CwlV from Paenibacillus polymyxa also has a similar fold (see PDB entry 1JWQ). |
|
Other databases
| PFAM | CL0035 |
|
| SCOP | 53187 |
