ArticleACS chemical biology2023
Chemoproteomics Reveals Disruption of Metal Homeostasis and Metalloproteins by the Antibiotic Holomycin.
Article in ACS chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 9 citations in OpenAlex.
- GTP hydrolysis-powered zinc metallochaperones as molecular switches.Current opinion in chemical biology · 2026Review
- Design, Synthesis, and Antitubercular Activity of Thiolutin-Cycloserine Hybrids: Reducing Cytotoxicity.Microorganisms · 2026Article
- Expanding the Chemoproteomic Toolkit to Asparagine and Glutamine.ACS chemical biology · 2026Article
- Biodiversity-Driven Natural Products and Bioactive Metabolites.Plants (Basel, Switzerland) · 2025Review
- Exploring Metalloproteome Remodeling in Calprotectin-StressedACS chemical biology · 2025Article
- Exploring metalloproteome remodeling in calprotectin-stressedbioRxiv : the preprint server for biology · 2025Article
- Reductive activation of the disulfide-containing antibiotic thiolutin is mediated by both bacillithiol and FAD-dependent disulfide reductases.Journal of bacteriology · 2025Article
- Dual Redox Targeting by Pyrroloformamide A and Silver Ions Enhances Antibacterial and Anti-Biofilm Activity Against Carbapenem-ResistantAntibiotics (Basel, Switzerland) · 2025Article
- Activation of Dithiolopyrrolone Antibiotics by Cellular Reductants.Biochemistry · 2025Article
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- Proteomic strategies to interrogate the Fe-S proteome.Biochimica et biophysica acta. Molecular cell research · 2024Review
- The Hybrid Antibiotic Thiomarinol A Overcomes Intrinsic Resistance inACS infectious diseases · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The natural product holomycin contains a unique cyclic ene-disulfide and exhibits broad-spectrum antimicrobial activities. Reduced holomycin chelates metal ions with a high affinity and disrupts metal homeostasis in the cell. To identify cellular metalloproteins inhibited by holomycin, reactive-cysteine profiling was performed using isotopic tandem orthogonal proteolysis-activity-based protein profiling (isoTOP-ABPP). This chemoproteomic analysis demonstrated that holomycin treatment increases the reactivity of metal-coordinating cysteine residues in several zinc-dependent and iron-sulfur cluster-dependent enzymes, including carbonic anhydrase II and fumarase A. We validated that holomycin inhibits fumarase A activity in bacterial cells and diminishes the presence of iron-sulfur clusters in fumarase A. Whole-proteome abundance analysis revealed that holomycin treatment induces zinc and iron starvation and cellular stress. This study suggests that holomycin inhibits bacterial growth by impairing the functions of multiple metalloenzymes and sets the stage for investigating the impact of metal-binding molecules on metalloproteomes by using chemoproteomics.
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Registered trials
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