Epigallocatechin gallate is a slow-tight binding inhibitor of enoyl-ACP reductase from Plasmodium falciparum

Banerjee, Tanushree and Sharma, Shailendra Kumar and Surolia, Avadhesha and Surolia, Namita (2008) Epigallocatechin gallate is a slow-tight binding inhibitor of enoyl-ACP reductase from Plasmodium falciparum. In: Biochemical and Biophysical Research Communications, 377 (4). pp. 1238-1242.

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Abstract

Epigallocatechin gallate (EGCG) is known to have numerous pharmacological properties. In the present study, we have shown that EGCG inhibits enoyl–acyl carrier protein reductase of Plasmodium falciparum (PfENR) by following a two-step, slow, tight-binding inhibition mechanism. The association/isomerization rate constant (k5) of the reversible and loose PfENR–EGCG binary complex to a tight [PfENR–EGCG]* or EI* complex was calculated to be 4.0 × 10−2 s−1. The low dissociation rate constant (k6) of the [PfENR–EGCG]* complex confirms the tight-binding nature of EGCG. EGCG inhibited PfENR with the overall inhibition constant (Ki*) of 7.0 ± 0.8 nM. Further, we also studied the effect of triclosan on the inhibitory activity of EGCG. Triclosan lowered the k6 of the EI* complex by 100 times, lowering the overall Ki* of EGCG to 97.5 ± 12.5 pM. The results support EGCG as a promising candidate for the development of tea catechin based antimalarial drugs.

Item Type:	Journal Article
Publication:	Biochemical and Biophysical Research Communications
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Keywords:	EGCG;Plasmodium falciparumMalaria;Enoyl-ACP reductase;Slow; Tight-binding inhibitor;PfENR;Triclosan
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	29 Mar 2010 11:46
Last Modified:	19 Sep 2010 05:57
URI:	http://eprints.iisc.ac.in/id/eprint/26291

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