6zja

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Helicobacter pylori urease with inhibitor bound in the active site

Structural highlights

6zja is a 24 chain structure with sequence from Helicobacter pylori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2Å
Ligands:DJM, KCX, NI
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

URE23_HELPY Ammonia produced by ureolysis increases the gastric pH thereby providing an environment permissive for colonization of the stomach.[1]

Publication Abstract from PubMed

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 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.

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Citations
2 reviews cite this structure
Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from <i>Helicobacter pylori</i> Next Generation Sequencing Data.
Vital et al. (2022)
1 more
12 other articles
No citations found

See Also

References

  1. ↑ Tsuda M, Karita M, Morshed MG, Okita K, Nakazawa T. A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach. Infect Immun. 1994 Aug;62(8):3586-9. PMID:8039935
  2. ↑ Cunha ES, Chen X, Sanz-Gaitero M, Mills DJ, Luecke H. Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution. Nat Commun. 2021 Jan 11;12(1):230. PMID:33431861 doi:10.1038/s41467-020-20485-6

Contents


PDB ID 6zja

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