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

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9973-9982
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number13
DOIs
Publication statusPublished - Mar 30 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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