title: Analysis of the mechanism of inhibition of human matrix metalloproteinase 7 (MMP-7) activity by green tea catechins.
abstract: 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-diaminopropionyl]-L-Ala-L-Arg-NH(2), the inhibitory effects of (-)-epigallocatechin-3-gallate (EGCG), (-)-gallocatechin-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 CaCl(2) concentrations from 10 to 50 mM. The fluorescence of EGCG and GCG decreased with increasing CaCl(2) 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.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyake
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yasukawa
authors.forename: Kuniyo
authors.initials: K
authors.lastname: Inouye
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002122:Calcium Chloride / Q000378:metabolism / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D002863:Chromogenic Compounds / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013662:Tea / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D002863:Chromogenic Compounds; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D011994:Recombinant Proteins; D013662:Tea; C417939:catechin gallate; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D002122:Calcium Chloride