Metalloproteinase

A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal.

Most metalloproteases require zinc, but some use cobalt. The metal ion is coordinated to the protein via three ligands. The ligands co-ordinating the metal ion can vary with histidine, glutamate, aspartate, lysine, and arginine.^{[clarification needed]} The fourth coordination position is taken up by a labile water molecule.

There are two subgroups of metalloproteinases:

• Exopeptidases, metalloexopeptidases (EC number: 3.4.17).
• Endopeptidases, metalloendopeptidases (3.4.24). Well known metalloendopeptidases include ADAM proteins and matrix metalloproteinases.

Metalloproteases are the most diverse of the four main protease types, with more than 50 families classified 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.^[1] 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.^[1]

Treatment with chelating agents such as EDTA leads to complete inactivation. EDTA is a metal chelator that removes zinc, which is essential for activity. They are also inhibited by the chelator orthophenanthroline.

See also

• Matrix metalloproteinase
• The Proteolysis Map

References

External links

• The MEROPS online database for peptidases and their inhibitors: Metallo Peptidases
• MeSH Metalloproteases
• Metalloproteinase at eMedicine Dictionary
• Proteopedia: Metalloproteases

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