ArticleeLife2014
GE23077 binds to the RNA polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 77 citations in OpenAlex.
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- Targeting Bacterial RNA Polymerase: Harnessing Simulations and Machine Learning to Design Inhibitors for Drug-Resistant Pathogens.Biochemistry · 2025Review
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.Journal of the American Chemical Society · 2025Article
- Single-molecule studies reveal the off-pathway early paused state intermediates as a target of streptolydigin inhibition of RNA polymerase and its dramatic enhancement by Gre factors.Nucleic acids research · 2025Article
- Actinomycetes - The Repertoire of Diverse Bioactive Chemical Molecules: From Structures to Antibiotics.Current topics in medicinal chemistry · 2025Review
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.bioRxiv : the preprint server for biology · 2024Article
- Chemistry and biology of specialized metabolites produced byNatural product reports · 2024Review
- Stabilizing Pseudouridimycin: Synthesis, RNA Polymerase Inhibitory Activity, and Antibacterial Activity of Dipeptide-Modified Analogues.ChemMedChem · 2024Article
- A Novel Natural Siderophore Antibiotic Conjugate Reveals a Chemical Approach to Macromolecule Coupling.ACS central science · 2023Article
- Pseudouridimycin-A Potent Nucleoside Inhibitor of the RNA Polymerase Beta Prime Subunit ofACS omega · 2023Article
- Review
- An Optimized Workflow for the Discovery of New Antimicrobial Compounds Targeting Bacterial RNA Polymerase Complex Formation.Antibiotics (Basel, Switzerland) · 2022Article
- Design, Synthesis, and Characterization of TNP-2198, a Dual-Targeted Rifamycin-Nitroimidazole Conjugate with Potent Activity against Microaerophilic and Anaerobic Bacterial Pathogens.Journal of medicinal chemistry · 2022Article
- Bacterial MerR family transcription regulators: activationby distortion.Acta biochimica et biophysica Sinica · 2022Review
- TSSr: an R package for comprehensive analyses of TSS sequencing data.NAR genomics and bioinformatics · 2021Article
- The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases.Nature communications · 2021Article
- Diverse and unified mechanisms of transcription initiation in bacteria.Nature reviews. Microbiology · 2021Review
- The origin and evolution of a distinct mechanism of transcription initiation in yeasts.Genome research · 2021Article
- Nucleotide Loading Modes of Human RNA Polymerase II as Deciphered by Molecular Simulations.Biomolecules · 2020Article
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17 authors at 2 institutions in 2 countries.
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Abstract
Using a combination of genetic, biochemical, and structural approaches, we show that the cyclic-peptide antibiotic GE23077 (GE) binds directly to the bacterial RNA polymerase (RNAP) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides, and thereby preventing transcription initiation. The target-based resistance spectrum for GE is unusually small, reflecting the fact that the GE binding site on RNAP includes residues of the RNAP active center that cannot be substituted without loss of RNAP activity. The GE binding site on RNAP is different from the rifamycin binding site. Accordingly, GE and rifamycins do not exhibit cross-resistance, and GE and a rifamycin can bind simultaneously to RNAP. The GE binding site on RNAP is immediately adjacent to the rifamycin binding site. Accordingly, covalent linkage of GE to a rifamycin provides a bipartite inhibitor having very high potency and very low susceptibility to target-based resistance. DOI: http://dx.doi.org/10.7554/eLife.02450.001.
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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.