ArticleThe Journal of biological chemistry2009
Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- New Mutants of Epsilon Toxin fromToxins · 2022Article
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Article
- Lung endothelial cells are sensitive to epsilon toxin from Clostridium perfringens.Veterinary research · 2020Article
- A small bioactive glycoside inhibits epsilon toxin and prevents cell death.Disease models & mechanisms · 2019Article
- Inhibition of Pore-Forming Proteins.Toxins · 2019Review
- Inhibition of bacterial toxin recognition of membrane components as an anti-virulence strategy.Journal of biological engineering · 2019Review
- A Novel Panel of Rabbit Monoclonal Antibodies and Their Diverse Applications Including Inhibition ofAntibodies (Basel, Switzerland) · 2018Article
- Inhibition of Clostridium perfringens epsilon toxin by β-cyclodextrin derivatives.International journal of pharmaceutics · 2017Article
- Review
- The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin.PLoS pathogens · 2015Article
- Identification of tyrosine 71 as a critical residue for the cytotoxic activity of Clostridium perfringens epsilon toxin towards MDCK cells.Journal of microbiology (Seoul, Korea) · 2015Article
- Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens.PloS one · 2014Article
- Review
- A low-toxic site-directed mutant of Clostridium perfringens ε-toxin as a potential candidate vaccine against enterotoxemia.Human vaccines & immunotherapeutics · 2013Article
- Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies.Protein science : a publication of the Protein Society · 2013Article
- Obstructing toxin pathways by targeted pore blockage.Chemical reviews · 2012Review
- Identification of amino acids important for binding of Clostridium perfringens epsilon toxin to host cells and to HAVCR1.Biochemistry · 2012Article
- Coenzyme depletion by members of the aerolysin family of pore-forming toxins leads to diminished ATP levels and cell death.Molecular bioSystems · 2012Article
- Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2.PloS one · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Clostridium perfringens epsilon-toxin is responsible for a severe, often lethal intoxication. In this study, we characterized dominant-negative inhibitors of the epsilon-toxin. Site-specific mutations were introduced into the gene encoding epsilon-toxin, and recombinant proteins were expressed in Escherichia coli. Paired cysteine substitutions were introduced at locations predicted to form a disulfide bond. One cysteine in each mutant was introduced into the membrane insertion domain of the toxin; the second cysteine was introduced into the protein backbone. Mutant proteins with cysteine substitutions at amino acid positions I51/A114 and at V56/F118 lacked detectable cytotoxic activity in a MDCK cell assay. Cytotoxic activity could be reconstituted in both mutant proteins by incubation with dithiothreitol, indicating that the lack of cytotoxic activity was attributable to the formation of a disulfide bond. Fluorescent labeling of the cysteines also indicated that the introduced cysteines participated in a disulfide bond. When equimolar mixtures of wild-type epsilon-toxin and mutant proteins were added to MDCK cells, the I51C/A114C and V56C/F118C mutant proteins each inhibited the activity of wild-type epsilon-toxin. Further analysis of the inhibitory activity of the I51C/A114C and V56C/F118C mutant proteins indicated that these proteins inhibit the ability of the active toxin to form stable oligomeric complexes in the context of MDCK cells. These results provide further insight into the properties of dominant-negative inhibitors of oligomeric pore-forming toxins and provide the basis for developing new therapeutics for treating intoxication by epsilon-toxin.
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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.