gelatinases

Gelatinases are a subgroup of matrix metalloproteinases (MMPs) that specialize in degrading gelatin (denatured collagen) and certain native collagens, particularly type IV collagen found in basement membranes. The two best characterized gelatinases are MMP-2 (gelatinase A) and MMP-9 (gelatinase B). They are zinc-dependent endopeptidases produced and secreted mainly as inactive proenzymes (pro-MMP-2 and pro-MMP-9) and become active through proteolytic cleavage in the extracellular environment.

Structurally, gelatinases share the common MMP architecture: a propeptide domain, a catalytic domain containing the zinc-binding motif HEXGHXXGXXH, and a hemopexin-like C-terminal domain that influences substrate specificity and interactions with tissue inhibitors. Activation of pro-MMP-2 and pro-MMP-9 involves cellular and proteolytic mechanisms; for example, MMP-2 activation on the cell surface often requires MT1-MMP (MMP-14) and the accessory protein TIMP-2, whereas MMP-9 can be activated by various proteases in inflammatory contexts. Regulation occurs at transcriptional, post-translational, and extracellular levels, including inhibition by tissue inhibitors of metalloproteinases (TIMPs).

Gelatinases participate in normal physiological processes such as tissue remodeling, wound healing, inflammation, and angiogenesis by remodeling the extracellular matrix and basement membranes. They are also implicated in pathological conditions, including cancer invasion and metastasis, chronic inflammatory diseases, and neurovascular disorders. Detection of gelatinase activity is commonly performed using gelatin zymography, which measures enzymatic activity in biological samples.