TY - JOUR
T1 - Structure and mechanism of Helicobacter pylori fucosyltransferase
T2 - A basis for lipopolysaccharide variation and inhibitor design
AU - Sun, Han Yu
AU - Lin, Sheng Wei
AU - Ko, Tzu Ping
AU - Pan, Jia Fu
AU - Liu, Chia Ling
AU - Lin, Chun Nan
AU - Wang, Andrew H.J.
AU - Lin, Chun Hung
PY - 2007/3/30
Y1 - 2007/3/30
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M610285200
DO - 10.1074/jbc.M610285200
M3 - Article
C2 - 17251184
AN - SCOPUS:34248186582
SN - 0021-9258
VL - 282
SP - 9973
EP - 9982
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -