Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase | Zendy

Subhashri Kundu | Zendy; Goran Biuković | Zendy; Gerhard Grüber | Zendy; Thomas Dick | Zendy

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Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase

Author(s) -

Subhashri Kundu,

Goran Biuković,

Gerhard Grüber,

Thomas Dick

Publication year - 2016

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.01291-16

Subject(s) - bedaquiline , tryptophan synthase , protein subunit , atp synthase , biochemistry , bacteria , tryptophan , biology , chemistry , microbiology and biotechnology , tuberculosis , enzyme , mycobacterium tuberculosis , medicine , amino acid , genetics , gene , pathology

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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