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Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-07-02 00:00:00 , DOI: 10.1021/acschembio.8b00271
Cedric Laguri 1 , Alba Silipo 2 , Alessandra M. Martorana 3 , Paul Schanda 1 , Roberta Marchetti 2 , Alessandra Polissi 3 , Antonio Molinaro 2 , Jean-Pierre Simorre 1
Affiliation  

Lipopolysaccharides (LPS) are complex glycolipids forming the outside layer of Gram-negative bacteria. Their hydrophobic and heterogeneous nature greatly hampers their structural study in an environment similar to the bacterial surface. We have studied LPS purified from E. coli and pathogenic P. aeruginosa with long O-antigen polysaccharides assembled in solution as vesicles or elongated micelles. Solid-state NMR with magic-angle spinning permitted the identification of NMR signals arising from regions with different flexibilities in the LPS, from the lipid components to the O-antigen polysaccharides. Atomic scale data on the LPS enabled the study of the interaction of gentamicin antibiotic bound to P. aeruginosa LPS, for which we could confirm that a specific oligosaccharide is involved in the antibiotic binding. The possibility to study LPS alone and bound to a ligand when it is assembled in membrane-like structures opens great prospects for the investigation of proteins and antibiotics that specifically target such an important molecule at the surface of Gram-negative bacteria.

中文翻译:

完整脂多糖内毒素的固态NMR研究

脂多糖(LPS)是形成革兰氏阴性细菌外层的复杂糖脂。它们的疏水性和异质性极大地妨碍了在类似于细菌表面的环境中进行结构研究。我们已经研究了从大肠杆菌和致病性铜绿假单胞菌中提纯的LPS,以及在溶液中组装成小泡或细长胶束的长O抗原多糖。带有魔角旋转的固态NMR可以识别NMR信号,该信号来自脂多糖(从脂质组分到O抗原多糖)具有不同柔韧性的区域。LPS上的原子尺度数据使研究庆大霉素抗生素与铜绿假单胞菌结合的相互作用成为可能LPS,我们可以确认特定的寡糖参与了抗生素的结合。当将LPS组装成膜状​​结构时,单独研究LPS并与配体结合的可能性为研究专门针对革兰氏阴性细菌表面上这种重要分子的蛋白质和抗生素打开了广阔的前景。
更新日期:2018-07-02
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