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TitleCryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 230, Year 2021
Publish dateJan 11, 2021
AuthorsEva S Cunha / Xiaorui Chen / Marta Sanz-Gaitero / Deryck J Mills / Hartmut Luecke /
PubMed AbstractInfection 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 linksNat Commun / PubMed:33431861 / PubMed Central
MethodsEM (single particle)
Resolution2.0 - 2.4 Å
Structure data

11233

6zja

EMDB-11233, PDB-6zja:
Helicobacter pylori urease with inhibitor bound in the active site
Method: EM (single particle) / Resolution: 2.0 Å

4629

6qsu

EMDB-4629, PDB-6qsu:
Helicobacter pylori urease with BME bound in the active site
Method: EM (single particle) / Resolution: 2.4 Å

Chemicals

ChemComp-NI:
NICKEL (II) ION

ChemComp-BME:
BETA-MERCAPTOETHANOL

ChemComp-HOH:
WATER

ChemComp-DJM:
2-{[1-(3,5-dimethylphenyl)-1H-imidazol-2-yl]sulfanyl}-N-hydroxyacetamide

Source
  • helicobacter pylori (bacteria)
KeywordsHYDROLASE / dodecamer / bi nickel center / enzyme / cytoplasm

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