title: Direct inhibition of matrix metalloproteinase-2 (MMP-2) by (-)-epigallocatechin-3-gallate: A possible role for the fibronectin type II repeats.
abstract: Matrix metalloproteinases (MMPs) -2 and -9, also called gelatinases, constitute a distinct subgroup within the MMP family of extracellular matrix remodeling proteases. Gelatinases are implicated in tumor cell invasion and metastasis, and are attractive therapeutic targets. Several synthetic small molecule inhibitors of MMPs developed till date have failed in clinical trials. This has prompted explorations into the gamut of dietary compounds and nutraceuticals for specific inhibitors of MMPs with desirable properties. (-)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, is popular as a potential chemotherapeutic agent with demonstrable anti-metastatic and MMP inhibitory activities. Here, we have addressed the mechanism of EGCG-mediated inhibition of MMP-2 using in silico molecular docking approach. We show for the first time that EGCG targets the fibronectin type II repeat regions 1 and 3 of MMP-2, binds amino acids that constitute the exosite of this enzyme and hinders proper positioning of the substrate. This study offers a novel insight into the inhibition of MMP-2 by EGCG and presents a starting point for development of novel therapeutic molecules that can specifically target the gelatinases.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
authors.forename: Shalinee
authors.initials: S
authors.lastname: Jha
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
authors.forename: Shankar Prasad
authors.initials: SP
authors.lastname: Kanaujia
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India. Electronic address: amul@iitg.ernet.in.
authors.forename: Anil M
authors.initials: AM
authors.lastname: Limaye
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry*; D008958:Models, Molecular; D020449:Repetitive Sequences, Amino Acid
chemical_list: D002392:Catechin; C045651:epigallocatechin gallate; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Epigallocatechin-3-gallate; Fibronectin type II repeat; Green tea polyphenol; Matrix metalloproteinase-2; Molecular docking