X-Ray Crystallography Reveals Potential Drug Target for Ulcer-Causing Bacteria


Half the world’s population is chronically infected with Helicobacter pylori, which causes gastritis, gastric ulcers, and an increased incidence of gastric adenocarcinoma. Treatment is becoming less effective because of increasing antibiotic resistance, suggesting that a specifically targeted approach to eradicate this organism would be beneficial. H.pylori’s survival and its ability to colonize in the acidic stomach depend on the presence of HpUreI, a proton-gated inner-membrane urea channel protein, which enables chemical reactions that balance acidic effects. HpUreI has thus been identified as a clinical target. An HpUreI structure, revealed at the Stanford Synchrotron Radiation Lightsource at the SLAC National Accelerator Laboratory, shows an arrangement of six protomers that form a compact hexameric ring about 95 Å in diameter and 45 Å in height. The hexamer’s center is filled with an ordered lipid plug. Each protomer encloses a channel of transmembrane helices, with specific side chains lining the entire channel, and defines two constriction sites in the middle of each channel. This first three-dimensional channel structure from the AmiS/UreI superfamily provides unique information that may guide the discovery of small-molecule inhibitors, offering the possibility of clinical treatment without the use of conventional antibiotics.


Strugatsky, D., et al. 2013. “Structure of the Proton-Gated Urea Channel from the Gastric Pathogen Helicobacter pylori,” Nature 493, 255–58. DOI: 10.1038/nature11684.