Peptidase_M6

• PFAM accession number: PF05547
• Interpro abstract (IPR008757):

  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 [ (PUBMED: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 [ (PUBMED:7674922) ].

  This group of metallopeptidases belong to MEROPS peptidase family M6 (immune inhibitor A family, clan MA(M)). The predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH.

  InhA of Bacillus thuringiensis (an entomopathogenic bacterium) specifically cleaves antibacterial peptides produced by insect hosts [ (PUBMED:2089225) ]. B. thuringiensis is highly resistant to the insect immune system due to its production of two factors, inhibitor A (InhA or InA) and inhibitor B (InhB or InB), which selectively block the humoral defence system developed by insects against Escherichia coli and Bacillus cereus [ (PUBMED:992874) ]. B. thuringiensis is especially resistant to cecropins and attacins, which are the main classes of inducible antibacterial peptides in various lepidopterans and dipterans [ (PUBMED:7140755) ], [ (PUBMED:3318666) ]. InhA has been shown to specifically hydrolyze cecropins and attacins in the immune hemolymph of Hyalophora cecropia (Cecropia moth) in vitro [ (PUBMED:6421577) ]. However, it has been suggested that the role of InhA in resistance to the humoral defence system is not consistent with the time course of InhA production [ (PUBMED:12029046) ].

  B. thuringiensis has two proteins belonging to this group (InhA and InhA2), and it has been shown that InhA2 has a vital role in virulence when the host is infected via the oral route [ (PUBMED:12029046) ]. The B. cereus member has been found as an exosporium component from endospores [ (PUBMED:10475957) ]. B. thuringiensis InhA is induced at the onset of sporulation and is regulated by Spo0A and AbrB [ (PUBMED:11429458) ]. Vibrio cholerae PrtV is thought to be encoded in the pathogenicity island [ (PUBMED:9371455) ]. However, PrtV mutants did not exhibit a reduced virulence phenotype, and thus PrtV is not an indispensable virulence factor [ (PUBMED:9371455) ].

  Annotation note: due to the presence of PKD repeats in some of the members of this group (e.g., V. cholerae VCA0223), spurious similarity hits may appear (involving unrelated proteins), which may lead to the erroneous transfer of functional annotations and protein names. Also, please note that related Bacillus subtilis Bacillopeptidase F (Bpr or Bpf) contains two different protease domains: N-terminal IPR000209 (peptidase S8, subtilase, a subtilisin-like serine protease) and this C-terminal domain (peptidase M6), which may also complicate annotation.

• GO process: proteolysis (GO:0006508)
• GO function: peptidase activity (GO:0008233)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry Peptidase_M6