ArticleThe Journal of biological chemistry2011
Tagetitoxin inhibits RNA polymerase through trapping of the trigger loop.
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 20 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
20 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting Bacterial RNA Polymerase: Harnessing Simulations and Machine Learning to Design Inhibitors for Drug-Resistant Pathogens.Biochemistry · 2025Review
- Rho-dependent transcription termination: a revisionist view.Transcription · 2021Review
- Total Synthesis of Tagetitoxin.Journal of the American Chemical Society · 2020Article
- The Mechanisms of Substrate Selection, Catalysis, and Translocation by the Elongating RNA Polymerase.Journal of molecular biology · 2019Review
- Active Center Control of Termination by RNA Polymerase III and tRNA Gene Transcription Levels In Vivo.PLoS genetics · 2016Article
- A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure.Trends in biochemical sciences · 2016Review
- Bacterial Transcription as a Target for Antibacterial Drug Development.Microbiology and molecular biology reviews : MMBR · 2016Review
- Bacterial RNA Polymerase-DNA Interaction-The Driving Force of Gene Expression and the Target for Drug Action.Frontiers in molecular biosciences · 2016Review
- Mapping the Escherichia coli transcription elongation complex with exonuclease III.Methods in molecular biology (Clifton, N.J.) · 2015Article
- CBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase.Nature communications · 2014Article
- Interplay between the trigger loop and the F loop during RNA polymerase catalysis.Nucleic acids research · 2014Article
- Tagetitoxin inhibits transcription by stabilizing pre-translocated state of the elongation complex.Nucleic acids research · 2013Article
- Energetic and structural details of the trigger-loop closing transition in RNA polymerase II.Biophysical journal · 2013Article
- The RNA polymerase trigger loop functions in all three phases of the transcription cycle.Nucleic acids research · 2013Article
- An insertion in the catalytic trigger loop gates the secondary channel of RNA polymerase.Journal of molecular biology · 2013Article
- Active site opening and closure control translocation of multisubunit RNA polymerase.Nucleic acids research · 2012Article
- Transcription initiation factor DksA has diverse effects on RNA chain elongation.Nucleic acids research · 2012Article
- Article
- The binding site and mechanism of the RNA polymerase inhibitor tagetitoxin: an issue open to debate.TranscriptionArticle
- Response to Klyuyev and Vassylyev: on the mechanism of tagetitoxin inhibition of transcription.TranscriptionArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tagetitoxin (Tgt) inhibits multisubunit chloroplast, bacterial, and some eukaryotic RNA polymerases (RNAPs). A crystallographic structure of Tgt bound to bacterial RNAP apoenzyme shows that Tgt binds near the active site but does not explain why Tgt acts only at certain sites. To understand the Tgt mechanism, we constructed a structural model of Tgt bound to the transcription elongation complex. In this model, Tgt interacts with the β' subunit trigger loop (TL), stabilizing it in an inactive conformation. We show that (i) substitutions of the Arg residue of TL contacted by Tgt confer resistance to inhibitor; (ii) Tgt inhibits RNAP translocation, which requires TL movements; and (iii) paused complexes and a "slow" enzyme, in which the TL likely folds into an altered conformation, are resistant to Tgt. Our studies highlight the role of TL as a target through which accessory proteins and antibiotics can alter the elongation complex dynamics.
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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.