Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/138536
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dc.contributor.authorSaw, Wuan-Geoken_US
dc.contributor.authorWu, Mu-Luen_US
dc.contributor.authorRagunathan, Priyaen_US
dc.contributor.authorBiuković, Goranen_US
dc.contributor.authorLau, Aik-Mengen_US
dc.contributor.authorShin, Joonen_US
dc.contributor.authorHarikishore, Amaravadhien_US
dc.contributor.authorCheung, Chen-Yien_US
dc.contributor.authorHards, Kielen_US
dc.contributor.authorSarathy, Jickky Palmaeen_US
dc.contributor.authorBates, Roderick Waylanden_US
dc.contributor.authorCook, Gregory M.en_US
dc.contributor.authorDick, Thomasen_US
dc.contributor.authorGrüber, Gerharden_US
dc.date.accessioned2020-05-08T01:13:15Z-
dc.date.available2020-05-08T01:13:15Z-
dc.date.issued2019-
dc.identifier.citationSaw, W.-G., Wu, M.-L., Ragunathan, P., Biuković, G., Lau, A.-M., Shin, J., . . . Grüber, G. (2019). Disrupting coupling within mycobacterial F-ATP synthases subunit ε causes dysregulated energy production and cell wall biosynthesis. Scientific Reports, 9, 16759-. doi:10.1038/s41598-019-53107-3en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttps://hdl.handle.net/10356/138536-
dc.description.abstractThe dynamic interaction of the N- and C-terminal domains of mycobacterial F-ATP synthase subunit ε is proposed to contribute to efficient coupling of H+-translocation and ATP synthesis. Here, we investigate crosstalk between both subunit ε domains by introducing chromosomal atpC missense mutations in the C-terminal helix 2 of ε predicted to disrupt inter domain and subunit ε-α crosstalk and therefore coupling. The ε mutant εR105A,R111A,R113A,R115A (ε4A) showed decreased intracellular ATP, slower growth rates and lower molar growth yields on non-fermentable carbon sources. Cellular respiration and metabolism were all accelerated in the mutant strain indicative of dysregulated oxidative phosphorylation. The ε4A mutant exhibited an altered colony morphology and was hypersusceptible to cell wall-acting antimicrobials suggesting defective cell wall biosynthesis. In silico screening identified a novel mycobacterial F-ATP synthase inhibitor disrupting ε’s coupling activity demonstrating the potential to advance this regulation as a new area for mycobacterial F-ATP synthase inhibitor development.en_US
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en_US
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en_US
dc.description.sponsorshipMOH (Min. of Health, S’pore)en_US
dc.language.isoenen_US
dc.relation.ispartofScientific Reportsen_US
dc.rights© 2019 The Author(s) (Nature Publishing Group). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.subjectScience::Biological sciences::Biochemistryen_US
dc.subjectScience::Biological sciences::Molecular biologyen_US
dc.titleDisrupting coupling within mycobacterial F-ATP synthases subunit ε causes dysregulated energy production and cell wall biosynthesisen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolSchool of Physical and Mathematical Sciencesen_US
dc.identifier.doi10.1038/s41598-019-53107-3-
dc.description.versionPublished versionen_US
dc.identifier.pmid31727946-
dc.identifier.scopus2-s2.0-85075033496-
dc.identifier.volume9en_US
dc.subject.keywordsBacteriologyen_US
dc.subject.keywordsPathogensen_US
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