Analysis of the Mechanism of Inhibition of Human Matrix Metalloproteinase 7 (MMP-7) Activity by Green Tea Catechins

Green tea catechins inhibit human matrix metalloproteinase 7 (MMP-7) activity non-competitively, and the galloyl group is essential for potent inhibition (Oneda et al., J. Biochem., 133, 571-576 (2003)). In this study, we analyzed the mechanism of this inhibition. In the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu-Gly-L-Leu-[N-3-(2,4-dinitrophenyl)-L-2,3-diamino- propionyl]-L-Ala-L-Arg-NH2, the inhibitory effects of (-)-epigallocatechin-3-gallate (EGCG), (-)-gallocate-chin-3-gallate (GCG), (-)-epicatechin-3-gallate (ECG), and (-)-catechin-3-gallate (CG) increased with increasing pH levels from 7.0 to 8.5. The inhibitory effects of EGCG and GCG were more potent than those of ECG and CG, and increased with increasing CaCl2 concentrations from 10 to 50 mM. The fluorescence of EGCG and GCG decreased with increasing CaCl2 concentrations and with the addition of MMP-7, while those of ECG and CG did not. Our results suggest that these differences result from that in the B ring, EGCG and GCG have phenol hydroxyl groups at the 3', 4', and 5' positions, while ECG and CG have them at the 3' and 4' positions.