title: Inhibition of pro-/active MMP-2 by green tea catechins and prediction of their interaction by molecular docking studies.
abstract: Matrix metalloproteinases (MMPs) play a crucial role in developing different types of lung diseases, e.g., pulmonary arterial hypertension (PAH). Green tea polyphenolic catechins such as EGCG and ECG have been shown to ameliorate various types of diseases including PAH. Our present study revealed that among the four green tea catechins (EGCG, ECG, EC, and EGC), EGCG and ECG inhibit pro-/active MMP-2 activities in pulmonary artery smooth muscle cell (PASMC) culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-2 with the green tea catechins by computational methods. In silico analysis revealed a strong interaction of pro-/active MMP-2 with EGCG/ECG, and galloyl group has been observed to be responsible for this interaction. The in silico analysis corroborated our experimental observation that EGCG and ECG are active in preventing both the proMMP-2 and MMP-2 activities. Importantly, these two catechins appeared to be better inhibitors for proMMP-2 in comparison to MMP-2 as revealed by gelatin zymogram and also by molecular docking studies. In many type of cells, activation of proMMP-2 occurs via an increase in the level of MT1-MMP (MMP-14). We, therefore, determined the interactions of MT1-MMP with the green tea catechins by molecular docking analysis. The study revealed a strong interaction of MT1-MMP with EGCG/ECG, and galloyl group has been observed to be responsible for the interaction.
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India.|Department of Biological Regulation, Weizmann Institute of Science, 76100, Rehovot, Israel.
authors.forename: Animesh
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India.
authors.forename: Suman Kumar
authors.initials: SK
authors.lastname: Nandy
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India.
authors.forename: Jaganmay
authors.initials: J
authors.lastname: Sarkar
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India.
authors.forename: Tapati
authors.initials: T
authors.lastname: Chakraborti
authors.affiliation: Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India. sajal_chakraborti@yahoo.com.
authors.forename: Sajal
authors.initials: S
authors.lastname: Chakraborti
mesh_terms: D000818:Animals; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013662:Tea / Q000737:chemistry*
chemical_list: D004792:Enzyme Precursors; D011480:Protease Inhibitors; D013662:Tea; D002392:Catechin; D018093:Gelatinases; C069860:progelatinase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Green tea catechin; MMP-2; MT1-MMP; Molecular docking analysis; PASMC; proMMP-2