Metalloproteinase

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Metalloproteinases (or metalloproteases) constitute a family of enzymes from the group of proteinases, classified by the nature of the most prominent functional group in their active site. There are two subgroups of metalloproteinases: metallocarboxypeptidases (EC number: 3.4.17) and metalloendopeptidases (3.4.24).

1 Types
2 Function
3 Clinical significance
4 See also
5 External links

[edit] Types

There are about 20 discovered MMPs which bear strong structural similarities to each other, namely about 40% of amino acid homology. Most of the MMPs have overlapping substrate specificity.

Important metalloproteinases are the bacterial enzyme thermolysin (which is a metalloendopeptidase), the digestive enzymes carboxypeptidase A or B (which are metallocarboxypeptidases), and the matrix metalloproteinases (MMP, also metalloendopeptidases).

[edit] Function

Metalloproteinases bind a metal ion such as Zn²⁺ or Ca²⁺ in their active site. The ion usually serves to coordinate two to four side chains and it is indispensable for the activity of the enzyme. The ion itself is also coordinated by a water molecule, which is also crucial for catalytical activity.

The metal ion in MMPs generally interacts with the incoming water molecule enhancing its reactivity and then stabilises the negative charge of the tetrahedral transition state to promote hydrolysis.

MMPs play an important role in tumor metastasis, embryonic development, wound healing - generally in processes including matrix degradation. The proper functioning of MMPs involves the binding of Ca and Zn ions as well, but only the latter is bound in the active site of the enzyme, while Ca is only required for maintaining the molecule's conformation.

[edit] Clinical significance

As MMPs promote cancer development their inhibitors (MMIs) should prevent it. One such drug is Marimastat but its use has not been altogether successful.