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Kinetic Determinants of the Interaction of Enoyl-ACP Reductase from Plasmodium falciparum with Its Substrates and Inhibitors

Kapoor, Mili and Dar, Jamal M and Surolia, Avadhesha and Surolia, Namita (2001) Kinetic Determinants of the Interaction of Enoyl-ACP Reductase from Plasmodium falciparum with Its Substrates and Inhibitors. In: Biochemical and Biophysical Research Communications, 289 (4). pp. 832-837.

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Abstract

We have recently demonstrated that Plasmodium falciparum, unlike its human host, has the type II fatty acid synthase, in which steps of fatty acid biosynthesis are catalyzed by independent enzymes. This difference could be successfully exploited in the design of drugs specifically targeted at the different enzymes of this pathway in P. falciparum, without affecting the corresponding enzymes in humans. The importance of enoyl-ACP reductase (FabI) in the fatty acid biosynthesis pathway makes it an important target in antimalarial therapy. We report here the initial characterization of Plasmodium FabI expressed in Escherichia coli. The $K_m$ values of the enzyme for crotonyl-CoA and NADH were derived as 165 and $33 \hspace{2mm} \mu M$, respectively. Triclosan shows competitive kinetics with respect to NADH but is uncompetitive with respect to $NAD^+$, which shows that the binding of triclosan to the enzyme is facilitated in the presence of $NAD^+$.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier.
Keywords: Enoyl-ACP reductase;Crotonyl-coenzyme A;Plasmodium falciparum;Triclosan;Fatty acid biosynthesis
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 09 Oct 2007
Last Modified: 19 Sep 2010 04:40
URI: http://eprints.iisc.ernet.in/id/eprint/12169

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