PROSITE documentation PDOC51694

Peptidase family M66 domain profile

The peptidase family M66 [E1] domain is a zinc metalloprotease found in:

• Enterohemorrhagic Escherichia coli (EHEC) neutral zinc metalloprotease StcE (EC 3.4.24.-).
• Aeromonas hydrophila ToxR-regulated lipoprotein TagA.
• Vibrio cholerae ToxR-activated gene A lipoprotein TagA (EC 3.4.24.-).

The peptidase family M66 domain adopts a characteristic mixed α+β and a conserved Met-turn (see <PDB:3UJZ>), features that place it within the metzincin superfamily of metalloproteases including astacins, ADAMs (a disintegrin and metalloprotease) (see <PDOC50215>) and matrixins. Notably, a central substrate-binding cleft containing the active site separates the peptidase family M66 domain into two subdomains SD1 and SD2. SD1 consists of a twisted β sheet packed on both sides by three helices. A sharp turn introduced by a conserved Gly in the zinc-binding motif along the active site helix then leads to SD2, which, after a series of convoluted loops, terminates in an helix. The peptidase family M66 coordinates an essential zinc ion in the characteristic tetrahedral fashion and possesses the extended zinc-binding motif HExxHxxGxxH [1].

The profile we developed covers the entire peptidase family M66 domain.