Structural Elucidation of the Mechanism for Inhibitor Resistance in the Na⁺-Translocating NADH-Ubiquinone Oxidoreductase from <i>Vibrio cholerae</i>.

ABSTRACT: Na⁺-translocating NADH-ubiquinone oxidoreductase (Na⁺-NQR) is a unique redox-driven Na⁺-pump. Since this enzyme is exclusively found in prokaryotes, including the human pathogens Vibrio cholerae and Neisseria gonorrhoeae, it is a promising target for highly selective antibiotics. Korormicin A, a natural product, and a specific and potent inhibitor of V. cholerae Na⁺-NQR, may become a lead compound for the relevant drug design. We previously showed that the G141A mutation in the NqrB subunit (NqrB-G141A) confers moderate resistance to korormicin A (about 100-fold). However, the efficiency of photoaffinity labeling of the mutant enzyme by a photoreactive korormicin derivative was the same as in the wild-type enzyme. Because of

SUBMITTER: Ishikawa-Fukuda M 

PROVIDER: S-EPMC12117499 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature