ArticleScientific reports2019
Fragment-based screening identifies inhibitors of ATPase activity and of hexamer formation of Cagα from the Helicobacter pylori type IV secretion system.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Type VIIb secretion systems in Lactobacillales: insights from streptococci and enterococci.Journal of bacteriology · 2026Review
- [Molecular mechanisms of chronic gastric mucosal inflammation induced byZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori.PLoS pathogens · 2026Article
- Beyond Urease: New Potential Enzymatic Targets inACS omega · 2026Review
- Unveiling a missing component of the atypical type IV secretion system required for natural transformation ofbioRxiv : the preprint server for biology · 2026Article
- Structural and functional diversity of type IV secretion systems.Nature reviews. Microbiology · 2024Review
- Roles of the components of theFuture microbiology · 2024Review
- Article
- Therapeutic effect of demethylated hydroxylated phillygenin derivative onFrontiers in microbiology · 2023Article
- Phillygenin InhibitsFrontiers in microbiology · 2022Article
- Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems.Frontiers in cellular and infection microbiology · 2022Review
- Design, synthesis, and evaluation of peptide-imidazo[1,2-a]pyrazine bioconjugates as potential bivalent inhibitors of the VirB11 ATPase HP0525.Journal of peptide science : an official publication of the European Peptide Society · 2021Article
- Type IV secretion systems: Advances in structure, function, and activation.Molecular microbiology · 2021Review
- Type IV Coupling Proteins as Potential Targets to Control the Dissemination of Antibiotic Resistance.Frontiers in molecular biosciences · 2020Review
- Inhibition of Type IV Secretion Activity and Growth ofFrontiers in cellular and infection microbiology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Type IV secretion systems are multiprotein complexes that mediate the translocation of macromolecules across the bacterial cell envelope. In Helicobacter pylori a type IV secretion system encoded by the cag pathogenicity island encodes 27 proteins and most are essential for virulence. We here present the identification and characterization of inhibitors of Cagα, a hexameric ATPase and member of the family of VirB11-like proteins that is essential for translocation of the CagA cytotoxin into mammalian cells. We conducted fragment-based screening using a differential scanning fluorimetry assay and identified 16 molecules that stabilize the protein suggesting that they bind Cagα. Several molecules affect binding of ADP and four of them inhibit the ATPase activity. Analysis of enzyme kinetics suggests that their mode of action is non-competitive, suggesting that they do not bind to the active site. Cross-linking suggests that the active molecules change protein conformation and gel filtration and transmission electron microscopy show that molecule 1G2 dissociates the Cagα hexamer. Addition of the molecule 1G2 inhibits the induction of interleukin-8 production in gastric cancer cells after co-incubation with H. pylori suggesting that it inhibits Cagα in vivo. Our results reveal a novel mechanism for the inhibition of the ATPase activity of VirB11-like proteins.
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