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Helicobacter pylori urease with inhibitor bound in the active site
Structural highlights
FunctionURE23_HELPY Ammonia produced by ureolysis increases the gastric pH thereby providing an environment permissive for colonization of the stomach.[1] Publication Abstract from PubMedInfection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of the world population will continue to be infected with this gastric pathogen. Current eradication, called triple therapy, entails a proton-pump inhibitor and two broadband antibiotics, however resistance to either clarithromycin or metronidazole is greater than 25% and rising. Therefore, there is an urgent need for a targeted, high-specificity eradication drug. Gastric infection by H. pylori depends on the expression of a nickel-dependent urease in the cytoplasm of the bacteria. Here, we report the 2.0 A resolution structure of the 1.1 MDa urease in complex with an inhibitor by cryo-electron microscopy and compare it to a beta-mercaptoethanol-inhibited structure at 2.5 A resolution. The structural information is of sufficient detail to aid in the development of inhibitors with high specificity and affinity. Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 A resolution.,Cunha ES, Chen X, Sanz-Gaitero M, Mills DJ, Luecke H Nat Commun. 2021 Jan 11;12(1):230. doi: 10.1038/s41467-020-20485-6. PMID:33431861[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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