Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase

The tuberculosis drug bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using the purified ε subunit of the synthase and spectroscopy, we previously demonstrated that the drug interacts with this protein near its unique tryptophan residue. Here, we show that replacement...

Full description

Saved in:
Bibliographic Details
Main Authors: Kundu, Subhashri, Biukovic, Goran, Grüber, Gerhard, Dick, Thomas
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2017
Subjects:
Online Access:https://hdl.handle.net/10356/83045
http://hdl.handle.net/10220/42376
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
Description
Summary:The tuberculosis drug bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using the purified ε subunit of the synthase and spectroscopy, we previously demonstrated that the drug interacts with this protein near its unique tryptophan residue. Here, we show that replacement of ε's tryptophan with alanine resulted in bedaquiline hypersusceptibility of the bacteria. Overexpression of the wild-type ε subunit caused resistance. These results suggest that the drug also targets the ε subunit.