ArticleACS chemical biology2012
Small-molecule inhibitors of bacterial AddAB and RecBCD helicase-nuclease DNA repair enzymes.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Antiphage defence systems Druantia III and Zorya II synergise via shared DNA intermediates in a phage-specific manner.bioRxiv : the preprint server for biology · 2026Article
- Chi hotspot control of RecBCD enzyme requires a RecB tether-RecC groove crosspoint interaction.Genetics · 2026Article
- Review
- Development of an inhibitor of the mutagenic SOS response that suppresses the evolution of quinolone antibiotic resistance.Chemical science · 2024Article
- Chi hotspot Control of RecBCD Helicase-nuclease: Enzymatic Tests Support the Intramolecular Signal-transduction Model.Journal of molecular biology · 2024Article
- RecBCD enzyme: mechanistic insights from mutants of a complex helicase-nuclease.Microbiology and molecular biology reviews : MMBR · 2023Review
- Established and Emerging Methods for Protecting Linear DNA in Cell-Free Expression Systems.Methods and protocols · 2023Review
- Cell-Free Display Techniques for Protein Evolution.Advances in biochemical engineering/biotechnology · 2023Article
- Article
- Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage.RSC medicinal chemistry · 2022Article
- Recombineering in Non-Model Bacteria.Current protocols · 2022Article
- Genomic Characterization of Twelve Lytic Bacteriophages Infecting Midgut Bacteria of Aedes aegypti.Current microbiology · 2022Article
- Defects in DNA double-strand break repair resensitize antibiotic-resistant Escherichia coli to multiple bactericidal antibiotics.MicrobiologyOpen · 2022Article
- Stress-Induced Mutagenesis, Gambler Cells, and Stealth Targeting Antibiotic-Induced Evolution.mBio · 2022Review
- Single-molecule studies of helicases and translocases in prokaryotic genome-maintenance pathways.DNA repair · 2021Review
- RexAB Promotes the Survival of Staphylococcus aureus Exposed to Multiple Classes of Antibiotics.Antimicrobial agents and chemotherapy · 2021Article
- Effective Use of Linear DNA in Cell-Free Expression Systems.Frontiers in bioengineering and biotechnology · 2021Review
- Article
- Flavodoxins as Novel Therapeutic Targets againstInternational journal of molecular sciences · 2020Review
- Article
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
The AddAB and RecBCD helicase-nucleases are related enzymes prevalent among bacteria but not eukaryotes and are instrumental in the repair of DNA double-strand breaks and in genetic recombination. Although these enzymes have been extensively studied both genetically and biochemically, inhibitors specific for this class of enzymes have not been reported. We developed a high-throughput screen based on the ability of phage T4 gene 2 mutants to grow in Escherichia coli only if the host RecBCD enzyme, or a related helicase-nuclease, is inhibited or genetically inactivated. We optimized this screen for use in 1536-well plates and screened 326,100 small molecules in the NIH molecular libraries sample collection for inhibitors of the Helicobacter pylori AddAB enzyme expressed in an E. coli recBCD deletion strain. Secondary screening used assays with cells expressing AddAB or RecBCD and a viability assay that measured the effect of compounds on cell growth without phage infection. From this screening campaign, 12 compounds exhibiting efficacy and selectivity were tested for inhibition of purified AddAB and RecBCD helicase and nuclease activities and in cell-based assays for recombination; seven were active in the 0.1-50 μM range in one or another assay. Compounds structurally related to two of these were similarly tested, and three were active in the 0.1-50 μM range. These compounds should be useful in further enzymatic, genetic, and physiological studies of these enzymes, both purified and in cells. They may also lead to useful antibacterial agents, since this class of enzymes is needed for successful bacterial infection of mammals.
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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.