Epigallocatechin-3-gallate binding to MMP-2 inhibits gelatinolytic activity without influencing the attachment to extracellular matrix proteins but enhances MMP-2 binding to TIMP-2.

Although epigallocatechin-3-gallate (EGCg), a dominant component of green tea catechins, has been demonstrated to have anti-gelatinase properties, the molecular mechanisms by which EGCg blocks gelatinolytic activities remain unknown. We investigated whether EGCg may affect matrix metalloproteinase-2 (MMP-2) binding to native and denatured-type I collagen, and binding to the tissue inhibitor of metalloproteinase-2 (TIMP-2). Here, we report that EGCg forms a reversible complex with MMP-2, resulting in the inhibition of gelatinolytic activity of MMP-2. EGCg had no effect on the MMP-2 binding to immobilized native and denatured-type I collagen, but significantly enhanced pro- and activated MMP-2 binding to TIMP-2, as assessed by immunoprecipitation. These findings provide a new understanding of the molecular mechanisms underlying the inhibitory effect of EGCg on the gelatinolytic activity of MMP-2.