Structure and mechanism of Helicobacter pylori fucosyltransferase: A basis for lipopolysaccharide variation and inhibitor design

Han Yu Sun, Sheng Wei Lin, Tzu Ping Ko, Jia Fu Pan, Chia Ling Liu, Chun Nan Lin, Andrew H.J. Wang, Chun Hung Lin

研究成果: 雜誌貢獻文章同行評審

98 引文 斯高帕斯(Scopus)

摘要

Helicobacter pylori α1,3-fucosyltransferase (FucT) is involved in catalysis to produce the Lewis x trisaccharide, the major component of the bacteria's lipopolysaccharides, which has been suggested to mimic the surface sugars in gastric epithelium to escape host immune surveillance. We report here three x-ray crystal structures of FucT, including the FucT·GDP-fucose and FucT·GDP complexes. The protein structure is typical of the glycosyltransferase-B family despite little sequence homology. We identified a number of catalytically important residues, including Glu-95, which serves as the general base, and Glu-249, which stabilizes the developing oxonium ion during catalysis. The residues Arg-195, Tyr-246, Glu-249, and Lys-250 serve to interact with the donor substrate, GDP-fucose. Variations in the protein and ligand conformations, as well as a possible FucT dimer, were also observed. We propose a catalytic mechanism and a model of polysaccharide binding not only to explain the observed variations in H. pylori lipopolysaccharides, but also to facilitate the development of potent inhibitors.

原文英語
頁(從 - 到)9973-9982
頁數10
期刊Journal of Biological Chemistry
282
發行號13
DOIs
出版狀態已發佈 - 3月 30 2007
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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