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

Arch Biochem Biophys. 2003 Jul 1;415(1):126-32. doi: 10.1016/s0003-9861(03)00221-2.

Abstract

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.

MeSH terms

  • Catechin / analogs & derivatives*
  • Catechin / chemistry*
  • Collagen Type I / chemistry*
  • Electrophoresis, Agar Gel / methods
  • Enzyme Activation
  • Extracellular Matrix Proteins / chemistry
  • Gelatin / chemistry
  • Gelatinases / antagonists & inhibitors
  • Gelatinases / chemistry*
  • Hydrolysis
  • Matrix Metalloproteinase 2 / chemistry*
  • Protein Binding
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Substrate Specificity
  • Tissue Inhibitor of Metalloproteinase-2 / chemistry*

Substances

  • Collagen Type I
  • Extracellular Matrix Proteins
  • Tissue Inhibitor of Metalloproteinase-2
  • Catechin
  • Gelatin
  • epigallocatechin gallate
  • Gelatinases
  • Matrix Metalloproteinase 2