Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2

Roy, Rana, Usha, Veeraraghavan, Kermani, Ali, Scott, David J., Hyde, Eva I., Besra, Gurdyal S., Alderwick, Luke J. and Fütterer, Klaus (2013) Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2. ACS chemical biology, 8 (10). pp. 2245-2255. ISSN 1554-8937

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Abstract

Recent evidence established that the cell envelope of Mycobacterium tuberculosis, the bacillus causing tuberculosis (TB), is coated by an α-glucan-containing capsule that has been implicated in persistence in a mouse infection model. As one of three known metabolic routes to α-glucan in mycobacteria, the cytoplasmic GlgE-pathway converts trehalose to α(1 → 4),α(1 → 6)-linked glucan in 4 steps. Whether individual reaction steps, catalyzed by trehalose synthase TreS, maltokinase Pep2, and glycosyltransferases GlgE and GlgB, occur independently or in a coordinated fashion is not known. Here, we report the crystal structure of M. tuberculosis TreS, and show by small-angle X-ray scattering and analytical ultracentrifugation that TreS forms tetramers in solution. Together with Pep2, TreS forms a hetero-octameric complex, and we demonstrate that complex formation markedly accelerates maltokinase activity of Pep2. Thus, complex formation may act as part of a regulatory mechanism of the GlgE pathway, which overall must avoid accumulation of toxic pathway intermediates, such as maltose-1-phosphate, and optimize the use of scarce nutrients.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/718660
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Biosciences
Identification Number: https://doi.org/10.1021/cb400508k
Depositing User: Scott, David
Date Deposited: 20 Apr 2017 12:47
Last Modified: 04 May 2020 16:39
URI: https://eprints.nottingham.ac.uk/id/eprint/41974

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