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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.
Original language | English |
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Pages (from-to) | 2245-2255 |
Journal | ACS chemical biology |
Volume | 8 |
Issue number | 10 |
Early online date | 31 Jul 2013 |
DOIs | |
Publication status | Published - 18 Oct 2013 |
Keywords
- macromolecular complex
- X-ray crystallography
- small angle X-ray
- analytical ultracentrifugation
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Dive into the research topics of 'Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2'. Together they form a unique fingerprint.Projects
- 1 Finished
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An integrated multi-disciplinary approach to unravel complex and essential cell wall biosynthetic pathways
1/01/08 → 30/06/13
Project: Research