ArticleThe Journal of antibiotics2017
Angucycline antibiotic waldiomycin recognizes common structural motif conserved in bacterial histidine kinases.
Article in The Journal of antibiotics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Pharmacophore-guided identification and dynamic characterization of potential binders of the sporulation histidine kinase KinA in Bacillus subtilis.Archives of microbiology · 2026Article
- Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.Molecular oral microbiology · 2026Review
- Allosteric coupling activation mechanism in histidine kinases.Scientific reports · 2025Article
- Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases.The Journal of antibiotics · 2024Article
- Microbial Genomics: Innovative Targets and Mechanisms.Antibiotics (Basel, Switzerland) · 2023Review
- Roles of Two-Component Signal Transduction Systems in Shigella Virulence.Biomolecules · 2022Review
- Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents.Frontiers in chemistry · 2022Review
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Host - Bacterial Pathogen Communication: The Wily Role of the Multidrug Efflux Pumps of the MFS Family.Frontiers in molecular biosciences · 2021Review
- Potential therapeutic approaches for a sleeping pathogen: tuberculosis a case for bioinorganic chemistry.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Review
- Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases.Nature communications · 2020Article
- The Signaling Molecule Indole Inhibits Induction of the AR2 Acid Resistance System inFrontiers in microbiology · 2020Article
- New natural products to meet the antibiotic crisis: a personal journey.The Journal of antibiotics · 2019Review
- Mzabimycins A and B, novel intracellular angucycline antibiotics produced bySaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Article
- The Two-Component Signaling System VraSRInfection and immunity · 2018Article
- Essential Two-Component Systems Regulating Cell Envelope Functions: Opportunities for Novel Antibiotic Therapies.The Journal of membrane biology · 2018Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two-component signal transduction systems (TCSs), composed of a histidine kinase sensor (HK) and its cognate response regulator, sense and respond to environmental changes and are related to the virulence of pathogens. TCSs are potential targets for alternative antibiotics and anti-virulence agents. Here we found that waldiomycin, an angucycline antibiotic that inhibits a growth essential HK, WalK, in Gram-positive bacteria, also inhibits several class I HKs from the Gram-negative Escherichia coli. NMR analyses and site-directed mutagenesis studies using the osmo-sensing EnvZ, a prototypical HK of E. coli, showed that waldiomycin directly binds to both H-box and X-region, which are the two conserved regions in the dimerization-inducing and histidine-containing phosphotransfer (DHp) domain of HKs. Waldiomycin inhibits phosphorylation of the conserved histidine in the H-box. Analysis of waldiomycin derivatives suggests that the angucyclic ring, situated near the H-box in the waldiomycin-EnvZ DHp domain complex model, is responsible for the inhibitory activity. We demonstrate that waldiomycin is an HK inhibitor binding to the H-box region and has the potential of inhibiting a broad spectrum of HKs.
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