2WZG

Legionella glucosyltransferase (Lgt1) crystal structure

2WZG の概要

• エントリーDOI: 10.2210/pdb2wzg/pdb
• 関連するPDBエントリー: 2WZF
• 分子名称: GLUCOSYLTRANSFERASE, MAGNESIUM ION, URIDINE-5'-DIPHOSPHATE-GLUCOSE, ... (4 entities in total)
• 機能のキーワード: transferase, elongation factor 1a, virulence factor, glucosyltransferase
• 由来する生物種: Legionella pneumophila
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60124.42

構造登録者

Hurtado-Guerrero, R.,Zusman, T.,Pathak, S.,Ibrahim, A.F.M.,Shepherd, S.,Prescott, A.,Segal, G.,Van Aalten, D.M.F. (登録日: 2009-11-29, 公開日: 2009-12-08, 最終更新日: 2024-05-08)

主引用文献

Hurtado-Guerrero, R.,Zusman, T.,Pathak, S.,Ibrahim, A.F.M.,Shepherd, S.,Prescott, A.,Segal, G.,Van Aalten, D.M.F.
Molecular Mechanism of Elongation Factor 1A Inhibition by a Legionella Pneumophila Glycosyltransferase.
Biochem.J., 426:281-, 2010

PubMed Abstract: Legionnaires' disease is caused by a lethal colonization of alveolar macrophages with the Gram-negative bacterium Legionella pneumophila. LpGT (L. pneumophila glucosyltransferase; also known as Lgt1) has recently been identified as a virulence factor, shutting down protein synthesis in the human cell by specific glucosylation of EF1A (elongation factor 1A), using an unknown mode of substrate recognition and a retaining mechanism for glycosyl transfer. We have determined the crystal structure of LpGT in complex with substrates, revealing a GT-A fold with two unusual protruding domains. Through structure-guided mutagenesis of LpGT, several residues essential for binding of the UDP-glucose-donor and EF1A-acceptor substrates were identified, which also affected L. pneumophila virulence as demonstrated by microinjection studies. Together, these results suggested that a positively charged EF1A loop binds to a negatively charged conserved groove on the LpGT structure, and that two asparagine residues are essential for catalysis. Furthermore, we showed that two further L. pneumophila glycosyltransferases possessed the conserved UDP-glucose-binding sites and EF1A-binding grooves, and are, like LpGT, translocated into the macrophage through the Icm/Dot (intracellular multiplication/defect in organelle trafficking) system.

PubMed: 20030628
DOI: 10.1042/BJ20091351

実験手法

X-RAY DIFFRACTION (1.9 Å)