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Title | Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 230, Year 2021 |
Publish date | Jan 11, 2021 |
Authors | Eva S Cunha / Xiaorui Chen / Marta Sanz-Gaitero / Deryck J Mills / Hartmut Luecke / |
PubMed Abstract | 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 ...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. |
External links | Nat Commun / PubMed:33431861 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.0 - 2.4 Å |
Structure data | EMDB-11233, PDB-6zja: |
Chemicals | ChemComp-NI: ChemComp-BME: ChemComp-HOH: ChemComp-DJM: |
Source |
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Keywords | HYDROLASE / dodecamer / bi nickel center / enzyme / cytoplasm |