Metalloproteinase

Metalloproteinases are a broad family of proteolytic enzymes that require a metal ion, typically zinc, at their active site to hydrolyze peptide bonds. The catalytic mechanism involves a coordinated zinc ion and a water molecule activated by a nearby residue, usually a conserved motif such as HExxHxxGxxH found in many members. Most metalloproteinases are secreted as inactive zymogens that require proteolytic activation to expose their active site.

The main groups are matrix metalloproteinases (MMPs), adisintegrin and metalloproteinases (ADAMs), and ADAM with thrombospondin motifs (ADAMTS). MMPs predominantly degrade extracellular matrix components such as collagen, elastin, and proteoglycans, facilitating tissue remodeling, development, and wound healing. ADAMs and ADAMTS cleave membrane-bound substrates and soluble proteins, regulating signaling pathways, receptor shedding, and matrix remodeling.

Regulation is tight and involves activation of latent proenzymes and inhibition by tissue inhibitors of metalloproteinases (TIMPs). Imbalance in metalloproteinase activity is linked to various diseases, including osteoarthritis, cancer invasion and metastasis, fibrosis, and cardiovascular disorders. Therapeutic strategies have pursued metalloproteinase inhibitors, but broad inhibition often caused adverse effects; current efforts emphasize selective targeting and localized delivery to mitigate side effects.

Beyond human physiology, metalloproteinases are present in many organisms and participate in processes ranging from digestion to pathogen virulence. Overall, they are essential mediators of protein turnover and tissue remodeling, with roles spanning normal biology and disease.