Diarylquinolines target subunit c of mycobacterial ATP synthase

被引：460

作者：

Koul, Anil

Dendouga, Najoua

Vergauwen, Karen

Molenberghs, Brenda

Vranckx, Luc

Willebrords, Rudy

Ristic, Zorica

Lill, Holger

Dorange, Ismet

Guillemont, Jerome

Bald, Dirk

Andries, Koen

机构：

[1] Tibotec BVBA, Dept Antimicrobial Res, B-2340 Beerse, Belgium

[2] Vrije Univ Amsterdam, Dept Biol Struct, Inst Mol Cell Biol, NL-1081 HV Amsterdam, Netherlands

[3] Johnson & Johnson, F-27106 Val De Reuil, France

来源：

NATURE CHEMICAL BIOLOGY | 2007年 / 3卷 / 06期

关键词：

D O I：

10.1038/nchembio884

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

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页码：323 / 324

页数：2

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