Diarylquinolines target subunit c of mycobacterial ATP synthase
Diarylquinolines target subunit c of mycobacterial ATP synthase
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DOI：
10.1038/nchembio884
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发表时间：
2007-06-01
影响因子：
14.8
通讯作者：
Andries, Koen
中科院分区：
文献类型：
--
作者：
Koul, Anil;Dendouga, Najoua;Andries, Koen
二芳基喹啉R207910（TMC 207）是用于治疗结核病的临床开发中有希望的候选物。尽管R207910耐药分枝杆菌在ATP合酶中存在突变，但该化合物的精确靶点尚不清楚。在这里，我们建立了遗传，生物化学和结合试验，ATP合酶的寡聚亚基C（AtpE）的目标是R207910。因此，靶向能量代谢是一种新的，有前途的抗菌药物发现的方法。
The diarylquinoline R207910 (TMC207) is a promising candidate in clinical development for the treatment of tuberculosis. Though R207910-resistant mycobacteria bear mutations in ATP synthase, the compound's precise target is not known. Here we establish by genetic, biochemical and binding assays that the oligomeric subunit c (AtpE) of ATP synthase is the target of R207910. Thus targeting energy metabolism is a new, promising approach for antibacterial drug discovery.