Collagen–Matrix Metalloproteinase interface (Collagen–MMP interface)

The Collagen–Matrix Metalloproteinase (MMP) interface refers to the specific structural interaction site between collagen triple helices and MMP enzymes, primarily the collagenases (MMP-1, MMP-8, MMP-13) and gelatinases (MMP-2, MMP-9). This interface is distinct from the catalytic active site and often involves the hemopexin-like (PEX) domain of the MMP, which is required for the recognition, binding, and unwinding of the collagen triple helix prior to cleavage. Targeting this interface is a therapeutic strategy designed to achieve high selectivity, as the PEX domains are more sequence-diverse than the highly conserved zinc-binding catalytic domains. By disrupting this protein-protein or protein-substrate interaction, inhibitors can prevent the degradation of specific collagen types involved in disease progression. This approach is particularly relevant in treating osteoarthritis, where MMP-13-mediated degradation of type II collagen is a key driver, and in oncology, where MMP-mediated matrix remodeling facilitates tumor invasion and metastasis. Selective inhibition of this interface aims to avoid the broad-spectrum toxicity, such as musculoskeletal syndrome, associated with early-generation MMP inhibitors.

Other names

MMP exositeHemopexin domain interfaceMMP-collagen binding siteCollagenase-collagen interaction site

Exosite inhibition preventing substrate recognition and triple-helix unwinding