Matrix metalloproteinases - MMPs
MMPs belong to a family of secreted or membrane-associated zinc endopeptidases capable of digesting extracellular matrix components.1-2
There are currently more than 25 family members that include collagenases (MMP-1, 8, 13, 18), gelatinases (MMP-2, 9), stromelysins (MMP-3, 10, 19), matrilysins (MMP-7 , 11, 26), and membrane-type MMPs (MMP-14 to 17, 24, 25).
MMPs are produced as pro-enzymes, which require an activation step to release the active MMPs. MMPs activity can be measured using FRET-based assays.
MMP-1 (collagenase-1) is involved in tumor development, metastasis and rheumatoid arthritis.3-5 MMP-1 is proposed as a therapeutic target for these diseases. It digests a broad range of substrates, including α-1 antitrypsin, myelin basic protein, collagen I, II, III, VII, VIII, casein, gelatin, and others. 3-5
MMP-9 (92-kDa gelatinase, collagenase-IV) is involved in a number of diseases such as cancer, angiogenesis, alopecia, and metastasis. 6-7 MMP-9 is secreted as zymogen with prodomain, gelatin-binding domain consisting of three contiguous fibronectin type II units, catalytic domain, proline-rich linker region, and C-terminal hemopexin-like domain. It can degrade a variety of substrates, including gelatin, collagens type IV, V, XIV, a2-macroglobulin, elastin, vitronectin, and proteoglycans.1,2,6,7
MMP-12 (macrophage elastase) is involved in smoke-induced emphysema, tumor and other diseases. 8-9 MMP-12 is secreted as a 54-kDa zymogen and becomes the mature 45-kDa active form after proteolytic cleavage. MMP-12 has a broad range of substrates, including α-1 proteinase inhibitor, α-2 antiplasmin, plasminogen activator inhibitor-2, collagen IV, laminin, fibronectin, elastin, but not interstitial collagens.8-9.
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6. Wilhelm, SM. et al. J. Biol.Chem. 264, 17213 (1989)
7. Fosang, AJ. et al., Biochem.J. 295, 273 (1993)
8. Hautamaki, D. et al. Science 277, 2002 (1997)
9. Dong, Z. et al. Cell 88, 801 (1997)