Combined effect of epigallocatechin gallate and triclosan on enoyl-ACP reductase of Mycobacterium tuberculosis |
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Authors: | Sharma Shailendra Kumar Kumar Gyanendra Kapoor Mili Surolia Avadhesha |
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Institution: | a Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India b National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India |
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Abstract: | 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 μM. 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 3H]EGCG and fluorescence titration assay support the spectrophotometric/kinetic inhibition data. The biochemical data has been explained by docking simulation studies. |
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Keywords: | Mycobacterium tuberculosis Tuberculosis InhA Enoyl reductase FAS I FAS II Tea catechins Epigallocatechin gallate EGCG Triclosan Fluorescence titration Scatchard plot |
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