Brief Communication abstract
Nature Chemical Biology 3, 323 - 324 (2007)
Published online: 13 May 2007 | doi:10.1038/nchembio884
Diarylquinolines target subunit c of mycobacterial ATP synthase
Anil Koul1,4, Najoua Dendouga1,4, Karen Vergauwen1, Brenda Molenberghs1, Luc Vranckx1, Rudy Willebrords1, Zorica Ristic2, Holger Lill2, Ismet Dorange3, Jerome Guillemont3, Dirk Bald2 & Koen Andries1
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.
- Department of Antimicrobial Research, Tibotec BVBA, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.
- Department of Structural Biology, Institute of Molecular Cell Biology, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
- Pharmaceutical Research & Development, Johnson & Johnson, Campus de Maigremont-BP615, F-27106 Val de Reuil Cedex, France.
- These authors contributed equally to this work.
Correspondence to: Anil Koul1,4 e-mail: akoul@prdbe.jnj.com
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