4LXF

Crystal structure of M. tuberculosis TreS

Summary for 4LXF

• Entry DOI: 10.2210/pdb4lxf/pdb
• Descriptor: Trehalose synthase, CALCIUM ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: (alpha/beta) barrel, amylase, isomerase, trehalose, maltose
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 142510.89

Authors

Roy, R.,Besra, G.S.,Futterer, K. (deposition date: 2013-07-29, release date: 2013-08-21, Last modification date: 2023-09-20)

Primary citation

Roy, R.,Usha, V.,Kermani, A.,Scott, D.J.,Hyde, E.I.,Besra, G.S.,Alderwick, L.J.,Futterer, K.
Synthesis of alpha-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2.
Acs Chem.Biol., 8:2245-2255, 2013

PubMed 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.

PubMed: 23901909
DOI: 10.1021/cb400508k

Experimental method

X-RAY DIFFRACTION (2.6 Å)