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...

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Detalles Bibliográficos
Autores principales: Kundu, Subhashri, Biukovic, Goran, Grüber, Gerhard, Dick, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2016
Materias:
Mechanisms of Action: Physiological Effects
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075122/
https://www.ncbi.nlm.nih.gov/pubmed/27620476
http://dx.doi.org/10.1128/AAC.01291-16
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author Kundu, Subhashri
Biukovic, Goran
Grüber, Gerhard
Dick, Thomas
author_facet Kundu, Subhashri
Biukovic, Goran
Grüber, Gerhard
Dick, Thomas
author_sort Kundu, Subhashri
collection PubMed
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.
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spelling pubmed-50751222016-11-11 Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase Kundu, Subhashri Biukovic, Goran Grüber, Gerhard Dick, Thomas Antimicrob Agents Chemother Mechanisms of Action: Physiological Effects 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. American Society for Microbiology 2016-10-21 /pmc/articles/PMC5075122/ /pubmed/27620476 http://dx.doi.org/10.1128/AAC.01291-16 Text en Copyright © 2016 Kundu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Action: Physiological Effects
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 Mechanisms of Action: Physiological Effects
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075122/
https://www.ncbi.nlm.nih.gov/pubmed/27620476
http://dx.doi.org/10.1128/AAC.01291-16
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