title: Expression cloning of cholesterol alpha-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori.
abstract: Helicobacter pylori infects over half the world's population, but only 3% of those infected develop peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. In H. pylori, alpha-glucosyl cholesterol constitutes more than 25% of cell wall lipids, and it has been suggested that alpha-glucosyl cholesterol is essential for H. pylori viability. Here, we identified cholesterol alpha-glucosyltransferase (CHLalphaGcT) using an expression cloning strategy and showed that this enzyme is distinctively inhibited by mucin-type O-glycans similar to those present in deeper portions of the gastric mucosa. Moreover, inactivation of CHLalphaGcT by homologous recombination led to H. pylori lethality. These results indicate that H. pylori CHLalphaGcT is a unique enzyme targeted by a natural antibiotic mucin and constitutes an excellent therapeutic target to prevent H. pylori-induced peptic ulcer, gastric carcinoma, and MALT lymphoma.
authors.affiliation: Glycobiology Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Heeseob
authors.initials: H
authors.lastname: Lee
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism*; D003001:Cloning, Molecular / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006023:Glycoproteins; C047874:gastric mucus glycoproteins; D002784:Cholesterol; D005964:Glucosyltransferases