Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587 – Nature

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  • Andries, K. et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307, 223–227 (2005).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Sutherland, H. S. et al. 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. Bioorg. Med. Chem. 27, 1292–1307 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luo, M. et al. Bedaquiline inhibits the yeast and human mitochondrial ATP synthases. Commun. Biol. 3, 452 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. Global Tuberculosis Report 2022 (WHO, 2022).

  • Perveen, S., Kumari, D., Singh, K. & Sharma, R. Tuberculosis drug discovery: progression and future interventions in the wake of emerging resistance. Eur. J. Med. Chem. 229, 114066 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Munro, S. A. et al. Patient adherence to tuberculosis treatment: a systematic review of qualitative research. PLoS Med. 4, e238 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koul, A. et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat. Chem. Biol. 3, 323–324 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Leibert, E., Danckers, M. & Rom, W. N. New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline. Ther. Clin. Risk Manag. 10, 597–602 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pym, A. S. et al. Bedaquiline in the treatment of multidrug-and extensively drug-resistant tuberculosis. Eur. Respir. J. 47, 564–574 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chesov, E. et al. Emergence of bedaquiline resistance in a high tuberculosis burden country. Eur. Respir. J. 59, 2100621 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guo, H. et al. Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline. Nature 589, 143–147 (2021).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Montgomery, M. G., Petri, J., Spikes, T. E. & Walker, J. E. Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis. Proc. Natl Acad. Sci. USA 118, e2111899118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Preiss, L. et al. Structure of the mycobacterial ATP synthase Fo rotor ring in complex with the anti-TB drug bedaquiline. Sci. Adv. 1, e1500106 (2015).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Courbon, G. M. et al. Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines. EMBO J. 42, e113687 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tran, S. L. & Cook, G. M. The F1Fo-ATP synthase of Mycobacterium smegmatis is essential for growth. J. Bacteriol. 187, 5023–5028 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gong, H. et al. An electron transfer path connects subunits of a mycobacterial respiratory supercomplex. Science 362, eaat8923 (2018).

    Article 
    ADS 
    PubMed 

    Google Scholar
     

  • Haagsma, A. C., Driessen, N. N., Hahn, M.-M., Lill, H. & Bald, D. ATP synthase in slow-and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction. FEMS Microbiol. Lett. 313, 68–74 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Harikishore, A. et al. Mutational analysis of mycobacterial F-ATP synthase subunit δ leads to a potent δ enzyme inhibitor. ACS Chem. Biol. 17, 529–535 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tantry, S. J. et al. Discovery of imidazo [1,2-a]pyridine ethers and squaramides as selective and potent inhibitors of mycobacterial adenosine triphosphate (ATP) synthesis. J. Med. Chem. 60, 1379–1399 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wong, C. F. et al. A systematic assessment of mycobacterial F1‐ATPase subunit ε’s role in latent ATPase hydrolysis. FEBS J. 288, 818–836 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hotra, A. et al. Discovery of a novel mycobacterial F‐ATP synthase inhibitor and its potency in combination with diarylquinolines. Angew. Chem. Int. Ed. Engl. 59, 13295–13304 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pethe, K. et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat. Med. 19, 1157–1160 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, S. et al. Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates. eLife 10, e69418 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koul, A. et al. Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism. Nat. Commun. 5, 3369 (2014).

    Article 
    ADS 
    PubMed 

    Google Scholar
     

  • Sassetti, C. M., Boyd, D. H. & Rubin, E. J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48, 77–84 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zimenkov, D. V. et al. Examination of bedaquiline-and linezolid-resistant Mycobacterium tuberculosis isolates from the Moscow region. J. Antimicrob. Chemother. 72, 1901–1906 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Martinez, E. et al. Mutations associated with in vitro resistance to bedaquiline in Mycobacterium tuberculosis isolates in Australia. Tuberculosis 111, 31–34 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Görbitz, C. H. Hydrogen-bond distances and angles in the structures of amino acids and peptides. Acta Crystallogr. B 45, 390–395 (1989).

    Article 
    ADS 

    Google Scholar
     

  • Guillemont, J., Meyer, C., Poncelet, A., Bourdrez, X. & Andries, K. Diarylquinolines, synthesis pathways and quantitative structure–activity relationship studies leading to the discovery of TMC207. Future Med. Chem. 3, 1345–1360 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lai, Y. et al. Structure of the human ATP synthase. Mol. Cell 83, 2137–2147 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vasanthakumar, T. et al. Structural comparison of the vacuolar and Golgi V-ATPases from Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 116, 7272–7277 (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721–745 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778–2786 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     



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