6Y3X

Crystal structure of the Francisella novicida lysine decarboxylase LdcF

6Y3X の概要

• エントリーDOI: 10.2210/pdb6y3x/pdb
• 分子名称: Lysine decarboxylase (1 entity in total)
• 機能のキーワード: lysine decarboxylase, oxidative stress resistance, lyase
• 由来する生物種: Francisella tularensis subsp. novicida
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 413201.01

構造登録者

Felix, J.,Siebert, C.,Gutsche, I.,Renesto, P. (登録日: 2020-02-19, 公開日: 2021-01-27, 最終更新日: 2024-01-24)

主引用文献

Felix, J.,Siebert, C.,Ducassou, J.N.,Nigou, J.,Garcia, P.S.,Fraudeau, A.,Huard, K.,Mas, C.,Brochier-Armanet, C.,Coute, Y.,Gutsche, I.,Renesto, P.
Structural and functional analysis of the Francisella lysine decarboxylase as a key actor in oxidative stress resistance.
Sci Rep, 11:972-972, 2021

PubMed Abstract: Francisella tularensis is one of the most virulent pathogenic bacteria causing the acute human respiratory disease tularemia. While the mechanisms underlying F. tularensis pathogenesis are largely unknown, previous studies have shown that a F. novicida transposon mutant with insertions in a gene coding for a putative lysine decarboxylase was attenuated in mouse spleen, suggesting a possible role of its protein product as a virulence factor. Therefore, we set out to structurally and functionally characterize the F. novicida lysine decarboxylase, which we termed LdcF. Here, we investigate the genetic environment of ldcF as well as its evolutionary relationships with other basic AAT-fold amino acid decarboxylase superfamily members, known as key actors in bacterial adaptative stress response and polyamine biosynthesis. We determine the crystal structure of LdcF and compare it with the most thoroughly studied lysine decarboxylase, E. coli LdcI. We analyze the influence of ldcF deletion on bacterial growth under different stress conditions in dedicated growth media, as well as in infected macrophages, and demonstrate its involvement in oxidative stress resistance. Finally, our mass spectrometry-based quantitative proteomic analysis enables identification of 80 proteins with expression levels significantly affected by ldcF deletion, including several DNA repair proteins potentially involved in the diminished capacity of the F. novicida mutant to deal with oxidative stress. Taken together, we uncover an important role of LdcF in F. novicida survival in host cells through participation in oxidative stress response, thereby singling out this previously uncharacterized protein as a potential drug target.

PubMed: 33441661
DOI: 10.1038/s41598-020-79611-5

実験手法

X-RAY DIFFRACTION (3.4 Å)