7APE

Crystal structure of LpqY from Mycobacterium thermoresistible in complex with trehalose

7APE の概要

• エントリーDOI: 10.2210/pdb7ape/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900006
• 分子名称: Lipoprotein (Sugar-binding) lpqY, alpha-D-glucopyranose-(1-1)-alpha-D-glucopyranose (3 entities in total)
• 機能のキーワード: lpqy, abc-transporter, trehalose complex, tuberculosis, transport protein
• 由来する生物種: Mycolicibacterium thermoresistibile
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98255.21

構造登録者

Furze, C.M.,Guy, C.M.,Angula, J.,Cameron, A.D.,Fullam, E. (登録日: 2020-10-16, 公開日: 2021-04-28, 最終更新日: 2024-10-16)

主引用文献

Furze, C.M.,Delso, I.,Casal, E.,Guy, C.S.,Seddon, C.,Brown, C.M.,Parker, H.L.,Radhakrishnan, A.,Pacheco-Gomez, R.,Stansfeld, P.J.,Angulo, J.,Cameron, A.D.,Fullam, E.
Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter.
J.Biol.Chem., 296:100307-100307, 2021

PubMed Abstract: The Mycobacterium tuberculosis (Mtb) LpqY-SugABC ATP-binding cassette transporter is a recycling system that imports trehalose released during remodeling 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, saturation transfer difference NMR, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the synthesis of trehalose analogs. 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 analogs and specifies a framework that can be exploited for the design of new antitubercular agents and/or diagnostic tools.

PubMed: 33476646
DOI: 10.1016/j.jbc.2021.100307

実験手法

X-RAY DIFFRACTION (1.7 Å)