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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.; Fütterer, Klaus

Authors

Rana Roy

Veeraraghavan Usha

Ali Kermani

David J. Scott

Eva I. Hyde

Gurdyal S. Besra

Luke J. Alderwick

Klaus Fütterer

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.

Journal Article Type Article
Publication Date Oct 18, 2013
Journal ACS chemical biology
Print ISSN 1554-8929
Electronic ISSN 1554-8937
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 8
Issue 10
Institution Citation Roy, R., Usha, V., Kermani, A., Scott, D. J., Hyde, E. I., Besra, G. S., …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), doi:10.1021/cb400508k
DOI https://doi.org/10.1021/cb400508k
Publisher URL http://pubs.acs.org/doi/abs/10.1021/cb400508k
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




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