Structure and Mechanism of Helicobacter pylori Fucosyltransferase-A BASIS FOR LIPOPOLYSACCHARIDE VARIATION AND INHIBITOR DESIGN
Resource
Journal of Biological Chemistry 282 (13): 9973-9982
Journal
Journal of Biological Chemistry
Pages
9973-9982
Date Issued
2007
Date
2007
Author(s)
Sun, Han-Yu
Lin, Sheng-Wei
Ko, Tzu-Ping
Pan, Jia-Fu
Liu, Chia-Ling
Lin, Chun-Nan
Wang, Andrew H.-J.
Lin, Chun-Hung
Abstract
Helicobacter pylori alpha1,3-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.
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