Diarylquinolines Target Subunit C of Mycobacterial ATP Synthase

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2007 May 15

PMID 17496888

Citations 207

Authors

Anil Koul

Najoua Dendouga

Karen Vergauwen

Brenda Molenberghs

Luc Vranckx

Rudy Willebrords

Zorica Ristic

Holger Lill

Ismet Dorange

Jerome Guillemont

Dirk Bald

Koen Andries

Affiliations

Soon will be listed here.

Abstract

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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