Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/163190
Title: Structure and regulation of the mycobacterial F1-ATPase
Authors: Wong, Chui Fann
Keywords: Science::Biological sciences::Biochemistry
Issue Date: 2022
Publisher: Nanyang Technological University
Source: Wong, C. F. (2022). Structure and regulation of the mycobacterial F1-ATPase. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/163190
Abstract: Tuberculosis 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.
URI: https://hdl.handle.net/10356/163190
DOI: 10.32657/10356/163190
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Theses

Files in This Item:
File Description SizeFormat 
Final Thesis.pdf11.25 MBAdobe PDFView/Open

Page view(s)

47
Updated on Feb 7, 2023

Download(s)

18
Updated on Feb 7, 2023

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.