Kinetic determinants of the interaction of enoyl-ACP reductase from Plasmodium falciparum with its substrates and inhibitors
Kinetic determinants of the interaction of enoyl-ACP reductase from Plasmodium falciparum with its substrates and inhibitors
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DOI：
10.1006/bbrc.2001.6061
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发表时间：
2001-12-14
影响因子：
3.1
通讯作者：
Surolia, N
中科院分区：
文献类型：
--
作者：
Kapoor, M;Dar, MJ;Surolia, N
我们最近证明，恶性疟原虫，不像它的人类宿主，有II型脂肪酸合酶，其中脂肪酸生物合成的步骤是由独立的酶催化。这种差异可以成功地用于设计专门针对恶性疟原虫中该途径的不同酶的药物，而不会影响人类中相应的酶。烯酰-ACP还原酶（FabI）在脂肪酸生物合成途径中的重要性使其成为抗疟治疗的重要靶点。我们在这里报告的初步表征疟原虫FabI在大肠杆菌中表达。该酶对巴豆酰辅酶A和NADH的Km值分别为165和33 μ M。三氯生对NADH表现出竞争性动力学，但对NAD（+）表现出非竞争性动力学，这表明在NAD（+）存在的情况下，三氯生与酶的结合得到促进。(C)2001年，爱思唯尔科学。
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 muM, 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(+). (C) 2001 Elsevier Science.