Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter

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. ISSN 0021-9258

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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: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 20 Jan 2021 00:57
Last Modified: 30 Sep 2021 16:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/78225
DOI: 10.1016/j.jbc.2021.100307

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