Biochemical and Biophysical Research Communications, Vol.368, No.1, 12-17, 2008
Combined effect of epigallocatechin gallate and triclosan on enoyl-ACP reductase of Mycobacterium tuberculosis
Among the various inhibitors known for enoyl-acyl carrier protein (ACP) reductases, triclosan and green tea catechins are two promising candidates. in the present study, we show, for the first time that epigallocatechin gallate (EGCG), a major component of green tea catechins, inhibits InhA, the enoyl-ACP reductase of Mycobacterium tuberculosis with an IC50 of 17.4 mu M. EGCG interferes with the binding of NADH to InhA. We also demonstrate that EGCG increased the inhibitory activity of triclosan towards InhA and vice-versa. Direct binding assay using [H-3]EGCG and fluorescence titration assay support the spectrophotometric/kinetic inhibition data. The biochemical data has been explained by docking simulation studies. (C) 2007 Elsevier Inc. All rights reserved.
Keywords:Mycobacterium tuberculosis;tuberculosis;InhA;enoyl reductase;FAS I;FAS III;tea catechins;epigallocatechin gallate;EGCG;triclosan;fluorescence titration;scatchard plot