| Type: | Domain | Name: | Peptidase M4 domain |
| Description: | Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role. Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site []. 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 [].This group of metallopeptidases that belong to the MEROPS peptidase family M4 (thermolysin family, clan MA(E)). The protein fold of the peptidase domain of thermolysin, is the type example for members of the clan MA. The thermolysin family is composed only of secreted eubacterial endopeptidases. The zinc-binding residues are H-142, H-146 and E-166, with E-143 acting as the catalytic residue.Thermolysin also contains 4 calcium-binding sites, which contribute to its unusual thermostability. The family also includes enzymes from a numberof pathogens, including Legionella and Listeria, and the protein pseudolysin, all with a substrate specificity for an aromatic residue in the P1' position. Three-dimensional structure analysis has shown that the enzymes undergoa hinge-bend motion during catalysis. Pseudolysin has a broader specificity, acting on large molecules such as elastin and collagen,possibly due to its wider active site cleft [].This entry represents a domain found in peptidase M4 family members. | Short Name: | Peptidase_M4_domain |
