Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution.
Eva S CunhaXiaorui ChenMarta Sanz-GaiteroDeryck J MillsHartmut LueckePublished in: Nature communications (2021)
Infection 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 Å resolution structure of the 1.1 MDa urease in complex with an inhibitor by cryo-electron microscopy and compare it to a β-mercaptoethanol-inhibited structure at 2.5 Å resolution. The structural information is of sufficient detail to aid in the development of inhibitors with high specificity and affinity.
Keyphrases
- helicobacter pylori
- helicobacter pylori infection
- electron microscopy
- single molecule
- endothelial cells
- randomized controlled trial
- poor prognosis
- high resolution
- cancer therapy
- health information
- breast cancer cells
- signaling pathway
- drug delivery
- bone marrow
- cell proliferation
- candida albicans
- mass spectrometry
- drug induced
- smoking cessation