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dc.contributor.authorWong, Chui Fannen_US
dc.identifier.citationWong, C. F. (2022). Structure and regulation of the mycobacterial F1-ATPase. Doctoral thesis, Nanyang Technological University, Singapore.
dc.description.abstractTuberculosis infection has been the leading cause of mortality due to the infectious agent Mycobacterium tuberculosis (Mtb). The prevalence of antibiotic-resistant strains drives a need to develop inhibitors that target essential complexes in Mtb. One such complex is the F1FO ATP synthase, composed of a H+-pumping Fo- and the catalytic F1 sector. The F-ATP synthase is essential for the viability of Mtb and has been validated as a drug-target. Unlike other bacteria, the mycobacterial F-ATP synthase possess latent ATP hydrolysis, which prevents changes in the proton motive force of the metabolically dormant pathogen. In this study, we addressed how mycobacteria reserves its ATP pools and elucidated the structural features contributing to the suppression of ATPase activity. Mutagenesis and biochemical studies unravelled epitopes in the α-, γ- and ε subunits, that contribute to latent ATP hydrolysis. Of interest, a mycobacterial specific C-terminal extension in the α-subunit was identified to be the major contributor towards ATP hydrolysis inhibition. A 3.5 Å determined cryo-EM structure of the F1-ATPase visualized that this extension inhibits the enzyme from hydrolysing ATP by preventing rotation of subunit γ as visualized in a single molecule assay. The ɑ-γ interaction epitope opened the door to unravel a new inhibitor.en_US
dc.publisherNanyang Technological Universityen_US
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).en_US
dc.subjectScience::Biological sciences::Biochemistryen_US
dc.titleStructure and regulation of the mycobacterial F1-ATPaseen_US
dc.typeThesis-Doctor of Philosophyen_US
dc.contributor.supervisorGerhard Gruberen_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.degreeDoctor of Philosophyen_US
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