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

Bibliographic Details
Main Authors: Kundu, Subhashri, Biukovic, Goran, Grüber, Gerhard, Dick, Thomas
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2017
Subjects:
Online Access:https://hdl.handle.net/10356/83045
http://hdl.handle.net/10220/42376
_version_ 1811678086892093440
author Kundu, Subhashri
Biukovic, Goran
Grüber, Gerhard
Dick, Thomas
author2 School of Biological Sciences
author_facet School of Biological Sciences
Kundu, Subhashri
Biukovic, Goran
Grüber, Gerhard
Dick, Thomas
author_sort Kundu, Subhashri
collection NTU
description 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.
first_indexed 2024-10-01T02:47:41Z
format Journal Article
id ntu-10356/83045
institution Nanyang Technological University
language English
last_indexed 2024-10-01T02:47:41Z
publishDate 2017
record_format dspace
spelling ntu-10356/830452023-02-28T17:00:09Z Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase Kundu, Subhashri Biukovic, Goran Grüber, Gerhard Dick, Thomas School of Biological Sciences F-ATP synthase ε subunit 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. NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Published version 2017-05-11T06:53:56Z 2019-12-06T15:10:48Z 2017-05-11T06:53:56Z 2019-12-06T15:10:48Z 2016 Journal Article Kundu, S., Biukovic, G., Grüber, G., & Dick, T. (2016). Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase. Antimicrobial Agents and Chemotherapy, 60(11), 6977-6979. 0066-4804 https://hdl.handle.net/10356/83045 http://hdl.handle.net/10220/42376 10.1128/AAC.01291-16 27620476 en Antimicrobial Agents and Chemotherapy © 2016 Kundu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. 3 p. application/pdf
spellingShingle F-ATP synthase
ε subunit
Kundu, Subhashri
Biukovic, Goran
Grüber, Gerhard
Dick, Thomas
Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
title Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
title_full Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
title_fullStr Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
title_full_unstemmed Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
title_short Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
title_sort bedaquiline targets the ε subunit of mycobacterial f atp synthase
topic F-ATP synthase
ε subunit
url https://hdl.handle.net/10356/83045
http://hdl.handle.net/10220/42376
work_keys_str_mv AT kundusubhashri bedaquilinetargetstheesubunitofmycobacterialfatpsynthase
AT biukovicgoran bedaquilinetargetstheesubunitofmycobacterialfatpsynthase
AT grubergerhard bedaquilinetargetstheesubunitofmycobacterialfatpsynthase
AT dickthomas bedaquilinetargetstheesubunitofmycobacterialfatpsynthase