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Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter
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Furze, Christopher M., Delso, Ignacio, Casal, Enriqueta, Guy, Collette S., Seddon, Chloe, Brown, Chelsea M., Parker, Hadyn L., Radhakrishnan, Anjana, Pacheco-Gomez, Raul, Stansfeld, Phillip J., Angulo, Jesus, Cameron, Alexander D. and Fullam, Elizabeth (2021) Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter. Journal of Biological Chemistry, 296 . 100307. doi:10.1016/j.jbc.2021.100307
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WRAP-Mycobacterium-tuberculosis-(Mtb)-LpqY-SugABC-ATP-binding-cassette-transporter-recycling-system-imports-trehalose-released-during-remodelling-Mtb-cell-envelope-Furze-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2173Kb) | Preview |
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WRAP-Mycobacterium-tuberculosis-(Mtb)-LpqY-SugABC-ATP-binding-cassette-transporter-recycling-system-imports-trehalose-released-during-remodelling-Mtb-cell-envelope-Furze-2021.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (9Mb) |
Official URL: http://dx.doi.org/10.1016/j.jbc.2021.100307
Abstract
The Mycobacterium tuberculosis (Mtb) LpqY-SugABC ATP-binding cassette transporter is a recycling system that imports trehalose released during remodelling of the Mtb cell-envelope. As this process is essential for the virulence of the Mtb pathogen it may represent an important target for tuberculosis drug and diagnostic development, but the transporter specificity and molecular determinants of substrate recognition are unknown. To address this, we have determined the structural and biochemical basis of how mycobacteria transport trehalose using a combination of crystallography, STD NMR, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays and the synthesis of trehalose analogues. This analysis pinpoints key residues of the LpqY substrate binding lipoprotein that dictate substrate-specific recognition and has revealed which disaccharide modifications are tolerated. These findings provide critical insights into how the essential Mtb LpqY-SugABC transporter reuses trehalose and modified analogues, and specifies a framework that can be exploited for the design of new anti-tubercular agents and/or diagnostic tools.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QP Physiology Q Science > QR Microbiology T Technology > TP Chemical technology |
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Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Mycobacterium tuberculosis , Trehalose , ATP-binding cassette transporters | ||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Journal of Biological Chemistry | ||||||||||||||||||||||||||||||||||||||||||
Publisher: | American Society for Biochemistry and Molecular Biology | ||||||||||||||||||||||||||||||||||||||||||
ISSN: | 0021-9258 | ||||||||||||||||||||||||||||||||||||||||||
Official Date: | 1 January 2021 | ||||||||||||||||||||||||||||||||||||||||||
Dates: |
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Date of first compliant deposit: | 3 February 2021 | ||||||||||||||||||||||||||||||||||||||||||
Volume: | 296 | ||||||||||||||||||||||||||||||||||||||||||
Article Number: | 100307 | ||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1016/j.jbc.2021.100307 | ||||||||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access | ||||||||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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