Peptidase M55, D-aminopeptidase (IPR007035)

Short name: Peptidase_M55

Overlapping homologous superfamilies

Family relationships


Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [PMID: 7674922]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [PMID: 7674922].

This group of metallopeptidases belong to MEROPS peptidase family M55 (DppA aminopeptidase family, clan MN). The type example is Bacillus subtilis DppA, which is a binuclear zinc-dependent, D-specific aminopeptidase. The structure reveals that DppA is an example of a self-compartmentalising protease, of which the proteasome is the most extensively studied. The DppA enzyme is composed of identical 30 kDa subunits organised in a decamer with 52 point-group symmetry. A 20 A wide channel runs through the complex, giving access to a central chamber holding the active sites. DppA and its homologues are characterized by the presence of the SXDXEG motif [PMID: 11473256]. The only known substrates are D-Ala-D-Ala and D-Ala-Gly-Gly.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.