Antimicrobial agents and chemotherapy, 2016-11, Vol.60 (11), p.6977-6979
2016
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Details
- Autor(en) / Beteiligte
- Titel
- Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase
- Ist Teil von
- Antimicrobial agents and chemotherapy, 2016-11, Vol.60 (11), p.6977-6979
- Ort / Verlag
- United States: American Society for Microbiology
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0066-4804eISSN: 1098-6596DOI: 10.1128/AAC.01291-16Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5075122
- Format
- –
- Schlagworte
- Adenosine Triphosphatases, Adenosine Triphosphatases - antagonists & inhibitors, Adenosine Triphosphatases - genetics, Alanine - genetics, Amino Acid Substitution, Antitubercular Agents, Antitubercular Agents - pharmacology, Diarylquinolines, Diarylquinolines - pharmacology, Enzyme Inhibitors, Enzyme Inhibitors - pharmacology, Mechanisms of Action: Physiological Effects, Microbial Sensitivity Tests, Molecular Targeted Therapy - methods, Mycobacterium, Mycobacterium smegmatis - drug effects, Mycobacterium smegmatis - genetics, Protein Subunits, Tryptophan - genetics