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

DOI: 10.1021/cb400508k DOI Help
PMID: 23901909 PMID Help

Authors: Rana Roy (University of Birmingham) , Veeraraghavan Usha (University of Birmingham) , Ali Kermani (University of Birmingham) , David J. Scott (University of Nottingham) , Eva I. Hyde (University of Birmingham) , Gurdyal S. Besra (University of Birmingham) , Luke Alderwick (University of Birmingham) , Klaus Fütterer (University of Birmingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Chemical Biology , VOL 8 (10)

State: Published (Approved)
Published: July 2013
Diamond Proposal Number(s): 6388

Open Access Open Access

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.

Diamond Keywords: Tuberculosis (TB); Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-Macromolecular Crystallography

Other Facilities: BM29 at ESRF

Added On: 06/08/2013 11:14


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)