The allosteric control mechanisms of alpha-glucan biosynthesis in bacteria
- D'ANGELO, CECILIA
- Marcelo Eduardo Guerin Director
- Javier Cifuentes Portocarrero Director
Defence university: Universidad del País Vasco - Euskal Herriko Unibertsitatea
Fecha de defensa: 03 October 2023
Type: Thesis
Abstract
The alpha-glucans, polysaccharides made of repetitive units of glucose, play a role as energy storage, as with intracellular glycogen, or as structural components, as with the capsular alpha-glucans surrounding the pathogenic Mycobacterium tuberculosis. Bacterial glycogen provides survival advantage during starvation periods whereas the mycobacterial capsule is critical in mediating host-pathogen interactions.The tetrameric enzyme ADP-glucose pyrophosphorylase (AGPase) catalyzes and controls: I) the initial step of glycogen biosynthesis and II) the synthesis of ADP-Glucose as precursor for the capsular alpha-glucanbio synthesis. In this work we disclose the cryoEM structures of the paradigmatic AGPase from Escherichia coli and Mycobacterium tuberculosis. The former, solved in the presence of the main positive and negative allosteric regulators, reveal distinct physiological conformational states that have different availability for ATP. Biochemical and microbiological evidence that support the latter show that single point-mutants in the catalytic and putative allosteric sites were unable to produce neither the product of reaction nor glycogen and the capsular alpha-glucans.