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.; F�tterer, Klaus

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.

Citation

Roy, R., Usha, V., Kermani, A., Scott, D. J., Hyde, E. I., Besra, G. S., Alderwick, L. J., & Fütterer, K. (2013). Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2. ACS Chemical Biology, 8(10), https://doi.org/10.1021/cb400508k

• Journal Article Type: Article
• Acceptance Date: Jul 31, 2013
• Online Publication Date: Jul 31, 2013
• Publication Date: Oct 18, 2013
• Deposit Date: Apr 20, 2017
• Publicly Available Date: Apr 20, 2017
• Journal: ACS chemical biology
• Print ISSN: 1554-8929
• Electronic ISSN: 1554-8937
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 10
• DOI: https://doi.org/10.1021/cb400508k
• Public URL: https://nottingham-repository.worktribe.com/output/718660
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/cb400508k
• Contract Date: Apr 20, 2017