Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2
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...
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| Format: | Article |
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American Chemical Society
2013
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| Online Access: | https://eprints.nottingham.ac.uk/41974/ |
| _version_ | 1848796391706460160 |
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| author | Roy, Rana Usha, Veeraraghavan Kermani, Ali Scott, David J. Hyde, Eva I. Besra, Gurdyal S. Alderwick, Luke J. Fütterer, Klaus |
| author_facet | Roy, Rana Usha, Veeraraghavan Kermani, Ali Scott, David J. Hyde, Eva I. Besra, Gurdyal S. Alderwick, Luke J. Fütterer, Klaus |
| author_sort | Roy, Rana |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:47:14Z |
| format | Article |
| id | nottingham-41974 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:47:14Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-419742020-05-04T16:39:19Z https://eprints.nottingham.ac.uk/41974/ 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 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. American Chemical Society 2013-10-18 Article PeerReviewed Roy, Rana, Usha, Veeraraghavan, Kermani, Ali, Scott, David J., Hyde, Eva I., Besra, Gurdyal S., Alderwick, Luke J. and Fütterer, Klaus (2013) Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2. ACS chemical biology, 8 (10). pp. 2245-2255. ISSN 1554-8937 http://pubs.acs.org/doi/abs/10.1021/cb400508k doi:10.1021/cb400508k doi:10.1021/cb400508k |
| spellingShingle | Roy, Rana Usha, Veeraraghavan Kermani, Ali Scott, David J. Hyde, Eva I. Besra, Gurdyal S. Alderwick, Luke J. Fütterer, Klaus Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2 |
| title | Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2 |
| title_full | Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2 |
| title_fullStr | Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2 |
| title_full_unstemmed | Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2 |
| title_short | Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2 |
| title_sort | synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase tres and maltokinase pep2 |
| url | https://eprints.nottingham.ac.uk/41974/ https://eprints.nottingham.ac.uk/41974/ https://eprints.nottingham.ac.uk/41974/ |