ZnMc

Zinc-dependent metalloprotease
ZnMc
SMART accession number:SM00235
Description: Neutral zinc metallopeptidases. This alignment represents a subset of known subfamilies. Highest similarity occurs in the HExxH zinc-binding site/ active site.
Interpro abstract (IPR006026):

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) ].

The majority of zinc-dependent metallopeptidases (with the notable exception of the carboxypeptidases) share a common pattern of primary structure [ (PUBMED:2914602) (PUBMED:1894005) ] in the part of their sequence involved in the binding of zinc, and can be grouped together as a superfamily,known as the metzincins, on the basis of this sequence similarity. They can be classified into around 40 distinct families [ (PUBMED:7674922) ].

This signature defines the metallopeptidases associated with MEROPS peptidase families: M7, M8, M10 (subfamilies A, B and C) and M12 (subfamily A) all of which are members of clan MA(M).

GO process:proteolysis (GO:0006508)
GO function:zinc ion binding (GO:0008270), metallopeptidase activity (GO:0008237)
Family alignment:
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There are 34425 ZnMc domains in 34168 proteins in SMART's nrdb database.

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