Matrix metalloproteinase-2, hemopexin domain (MMP-2, hemopexin domain)

The hemopexin domain of matrix metalloproteinase-2 (MMP-2) is a C-terminal, four-bladed β-propeller structure critical for substrate specificity, dimerization, and protein–protein interactions[1][3][4]. MMP-2, also known as gelatinase A, is a secreted, zinc-dependent endopeptidase that degrades components of the extracellular matrix (notably type IV collagen). The hemopexin domain is required for collagen triple helix degradation, efficient assembly and activation of the enzyme, and tissue invasion[3][4]. Mutations affecting this domain can lead to severe developmental phenotypes such as multicentric osteolysis, nodulosis, and arthropathy (MONA syndrome)[4]. Pharmacological inhibition of the hemopexin domain is an emerging strategy to achieve greater specificity in targeting MMP-2’s pathological roles in cancer, fibrosis, and vascular disease, while potentially reducing the adverse effects observed with broad-spectrum MMP inhibition[2].

Other names

MMP-2 hemopexin domainGelatinase A hemopexin domain72 kDa type IV collagenase hemopexin domain

Inhibition of proteolytic activity (by chelating zinc or binding the active site); Allosteric inhibition or direct binding to the hemopexin domain (modulates substrate binding and dimerization, emerging therapeutic strategy); Interference with protein–protein interactions (blocking hemopexin-mediated substrate specificity and tissue invasion)