Synthesis of 伪-Glucan in Mycobacteria Involves a Hetero-octameric Complex of Trehalose Synthase TreS and Maltokinase Pep2

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• 作者：Rana Roy ; Veeraraghavan Usha ; Ali Kermani ; David J. Scott ; Eva I. Hyde ; Gurdyal S. Besra ; Luke J. Alderwick ; Klaus F眉tterer
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：October 18, 2013
• 年：2013
• 卷：8
• 期：10
• 页码：2245-2255
• 全文大小：511K
• 年卷期：v.8,no.10(October 18, 2013)
• ISSN：1554-8937

文摘

Recent evidence established that the cell envelope of Mycobacterium tuberculosis, the bacillus causing tuberculosis (TB), is coated by an 伪-glucan-containing capsule that has been implicated in persistence in a mouse infection model. As one of three known metabolic routes to 伪-glucan in mycobacteria, the cytoplasmic GlgE-pathway converts trehalose to 伪(1 鈫?4),伪(1 鈫?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.