Metaloproteinasasas

Metaloproteinasasas is a term used to describe a broad class of proteolytic enzymes that require a metal ion, most commonly zinc, for catalysis. The best-characterized members are matrix metalloproteinases (MMPs), which hydrolyze extracellular matrix proteins such as collagens, gelatin, elastin, and proteoglycans. Other families within this group include the ADAMs and ADAMTSs (a disintegrin and metalloproteinase) and the astacins, as well as various venom and developmental metalloproteinases. Most MMPs are secreted as inactive proenzymes and require proteolytic removal of a propeptide to become active; this latent state is maintained by a cysteine residue that coordinates with the catalytic zinc, a mechanism known as the cysteine switch. The catalytic site typically contains a zinc-binding motif with a conserved HExGHxxGxxH sequence, and some MMPs possess additional domains, such as a hemopexin-like domain, which influences substrate specificity and interactions. Membrane-type MMPs (MT-MMPs) are anchored to the cell surface and can activate other MMPs, amplifying proteolysis.

Physiological roles include tissue remodeling, wound healing, embryonic development, and angiogenesis, as well as modulation of inflammation through processing of cytokines and receptors. Dysregulation of metalloproteinases is linked to diseases such as osteoarthritis, cancer invasion and metastasis, fibrosis, and cardiovascular disorders. Regulation occurs at multiple levels: gene expression, activation of latent enzymes, and inhibition by tissue inhibitors of metalloproteinases (TIMPs). Therapeutic strategies have aimed to inhibit these enzymes, but broad-spectrum inhibitors have faced limited clinical success due to side effects.