Identification of new inhibitors for alternative NADH dehydrogenase (NDH-II)
Identification of new inhibitors for alternative NADH dehydrogenase (NDH-II)
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DOI：
10.1111/j.1574-6968.2008.01451.x
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发表时间：
2009-02-01
影响因子：
2.1
通讯作者：
Kita, Kiyoshi
中科院分区：
文献类型：
--
作者：
Mogi, Tatsushi;Matsushita, Kazunobu;Kita, Kiyoshi
在细菌膜和植物、真菌和原生生物线粒体中，NADH脱氢酶（NDH-II）作为另一种NADH：醌还原酶，一种与膜表面结合的非质子泵单亚基酶。由于NDH-II在哺乳动物线粒体中不存在，因此它是新抗生素的一个有希望的靶点。然而，NDH-II的抑制剂是罕见的和非特异性的。利用氧化葡糖醛酸菌呼吸链结构简单的特点，我们对天然化合物进行了筛选，确定了东莨菪碱和短杆菌肽S为氧化葡糖醛酸菌的抑制剂。氧化丹NDH-II.此外，我们研究了它们对作为模型病原体酶的耻垢分枝杆菌和约氏疟原虫NDH-II的影响。
In bacterial membranes and plant, fungus and protist mitochondria, NADH dehydrogenase (NDH-II) serves as an alternative NADH : quinone reductase, a non-proton-pumping single-subunit enzyme bound to the membrane surface. Because NDH-II is absent in mammalian mitochondria, it is a promising target for new antibiotics. However, inhibitors for NDH-II are rare and unspecific. Taking advantage of the simple organization of the respiratory chain in Gluconobacter oxydans, we carried out screening of natural compounds and identified scopafungin and gramicidin S as inhibitors for G. oxydans NDH-II. Further, we examined their effects on Mycobacterium smegmatis and Plasmodium yoelii NDH-II as model pathogen enzymes.