ArticleThe Journal of biological chemistry2011
Cisplatin inhibits protein splicing, suggesting inteins as therapeutic targets in mycobacteria.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- A protein chaperone can stabilize the intein-containing precursor to indirectly promote protein splicing.Protein science : a publication of the Protein Society · 2026Article
- Designing a Whole-Cell Biosensor for Detection of Toxic Metals Using Intein Splicing Inhibition ofACS omega · 2026Article
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Effect of insertion of intein to Cryptococcus amylolentus, a nonpathogenic fungus closely related to causative agents of cryptococcosis.Microbial pathogenesis · 2025Article
- Conditional protein splicing of the Mycobacterium tuberculosis RecA intein in its native host.Scientific reports · 2024Article
- Conditional protein splicing of thebioRxiv : the preprint server for biology · 2024Article
- Half-Sandwich Type Platinum-Group Metal Complexes ofMolecules (Basel, Switzerland) · 2023Article
- Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria.Frontiers in chemistry · 2023Article
- Calcimycin InhibitsACS infectious diseases · 2022Article
- Article
- SufB intein splicing in Mycobacterium tuberculosis is influenced by two remote conserved N-extein histidines.Bioscience reports · 2022Article
- Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands.Frontiers in chemistry · 2022Article
- Inteins as Drug Targets and Therapeutic Tools.Frontiers in molecular biosciences · 2022Review
- Reactive Chlorine Species Reversibly Inhibit DnaB Protein Splicing in Mycobacteria.Microbiology spectrum · 2021Article
- The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling.Molecular medicine (Cambridge, Mass.) · 2021Review
- Construction and Quantitation of a Selectable Protein Splicing Sensor Using Gibson Assembly and Spot Titers.Current protocols · 2021Article
- Small-molecule inhibitors for the Prp8 intein as antifungal agents.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Intein Inhibitors as Novel Antimicrobials: Protein Splicing in Human Pathogens, Screening Methods, and Off-Target Considerations.Frontiers in molecular biosciences · 2021Review
- Gold Nanoparticles Augment N-Terminal Cleavage and Splicing Reactions inFrontiers in bioengineering and biotechnology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis harbors three protein splicing elements, called inteins, in critical genes and their protein products. Post-translational removal of the inteins occurs autocatalytically and is required for function of the respective M. tuberculosis proteins. Inteins are therefore potential targets for antimycobacterial agents. In this work, we report that the splicing activity of the intein present in the RecA recombinase of M. tuberculosis is potently inhibited by the anticancer drug cisplatin (cis-diamminedichloro-platinum(II)). This previously unrecognized activity of cisplatin was established using both an in vitro intein splicing assay, which yielded an IC(50) of ∼2 μM, and a genetic reporter for intein splicing in Escherichia coli. Testing of related platinum(II) complexes indicated that the inhibition activity is highly structure-dependent, with cisplatin exhibiting the best inhibitory effect. Finally, we report that cisplatin is toxic toward M. tuberculosis with a minimum inhibitory concentration of ∼40 μM, and in genetic experiments conducted with the related Mycobacterium bovis bacillus Calmette-Guérrin (BCG) strain, we show that cisplatin toxicity can be mitigated by intein overexpression. We propose that cisplatin inhibits intein activity by modifying at least one conserved cysteine residue that is required for splicing. Together these results identify a novel active site inhibitor of inteins and validate inteins as viable targets for small molecule inhibition in mycobacteria.
Indexed as
Identifiers
What OpenQuestion holds
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.