The domain within your query sequence starts at position 500 and ends at position 657; the E-value for the Peptidase_M43 domain shown below is 2.5e-10.



PFAM accession number:PF05572
Interpro abstract (IPR008754):

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 the MEROPS peptidase M43 (cytophagalysin family, clan MA(M)), subfamily M43. The zinc ligands and active site residue for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH. This model includes pappalysins and related metalloprotease domains from all three kingdoms of life. The three-dimensional structure of an archaeal representative, ulilysin (MEROPS identifier M43.007), has been solved [ (PUBMED:16627477) ].

The type example of this family is the pregnancy-associated plasma protein A (PAPP-A; MEROPS identifier M43.004), which cleaves insulin-like growth factor (IGF) binding protein-4 (IGFBP-4), causing a dramatic reduction in its affinity for IGF-I and -II. Through this mechanism, PAPP-A is a regulator of IGF bioactivity in several systems, including the Homo sapiens ovary and the cardiovascular system [ (PUBMED:10913121) (PUBMED:11713222) (PUBMED:11897673) (PUBMED:11161967) ].

This is a PFAM domain. For full annotation and more information, please see the PFAM entry Peptidase_M43