ArticleToxins2018
Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding.
Article in Toxins, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Biophysical and Biochemical Assays for Screening Small Molecule Inhibitors Targeting Toxin-Ribosome Interactions.Toxins · 2026Review
- A fluorescence anisotropy-based competition assay to identify inhibitors against ricin and Shiga toxin ribosome interactions.Analytical biochemistry · 2024Article
- A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication.bioRxiv : the preprint server for biology · 2024Article
- Article
- Structure-Function Analysis of the A1 Subunit of Shiga Toxin 2 with Peptides That Target the P-Stalk Binding Site and Inhibit Activity.Biochemistry · 2024Article
- Structure-based design and optimization of a new class of small molecule inhibitors targeting the P-stalk binding pocket of ricin.Bioorganic & medicinal chemistry · 2024Article
- Analysis of the Sequence Preference of Saporin by Deep Sequencing.ACS chemical biology · 2022Article
- Synthesis and Structural Characterization of Ricin Inhibitors Targeting Ribosome Binding Using Fragment-Based Methods and Structure-Based Design.Journal of medicinal chemistry · 2021Article
- Structural basis for the interaction of Shiga toxin 2a with a C-terminal peptide of ribosomal P stalk proteins.The Journal of biological chemistry · 2020Article
- Small Molecule Inhibitors Targeting the Interaction of Ricin Toxin A Subunit with Ribosomes.ACS infectious diseases · 2020Article
- Introduction to theToxins · 2019Article
- Leucine 232 and hydrophobic residues at the ribosomal P stalk binding site are critical for biological activity of ricin.Bioscience reports · 2019Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Ricin A chain (RTA) depurinates the sarcin/ricin loop (SRL) by interacting with the C-termini of the ribosomal P stalk. The ribosome interaction site and the active site are located on opposite faces of RTA. The interaction with P proteins allows RTA to depurinate the SRL on the ribosome at physiological pH with an extremely high activity by orienting the active site towards the SRL. Therefore, if an inhibitor disrupts RTA⁻ribosome interaction by binding to the ribosome binding site of RTA, it should inhibit the depurination activity. To test this model, we synthesized peptides mimicking the last 3 to 11 amino acids of P proteins and examined their interaction with wild-type RTA and ribosome binding mutants by Biacore. We measured the inhibitory activity of these peptides on RTA-mediated depurination of yeast and rat liver ribosomes. We found that the peptides interacted with the ribosome binding site of RTA and inhibited depurination activity by disrupting RTA⁻ribosome interactions. The shortest peptide that could interact with RTA and inhibit its activity was four amino acids in length. RTA activity was inhibited by disrupting its interaction with the P stalk without targeting the active site, establishing the ribosome binding site as a new target for inhibitor discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.