ArticleNature communications2024
Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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
12 citing papers in PubMed.
- Ribosome remodeling drives translation adaptation during viral infection and cellular stress.Molecular cell · 2026Article
- Off-target anti-leukemic effects of antibiotics: mechanisms and therapeutic insights.Cancer chemotherapy and pharmacology · 2026Review
- Mechanisms and disease relevance of mitochondrial translation in humans.Nature reviews. Molecular cell biology · 2026Review
- Dual site targeting of the bacterial 70S ribosome by tetracyclines.Nature communications · 2026Article
- NAA40 and NAC cooperate in co-translational histone acetylation in humans.Nature communications · 2026Article
- Pleiotropic regulation of mitochondrial translational factors in governing proliferation, apoptosis and metastasis during cancer progression.World journal of clinical oncology · 2026Review
- Structural basis of co-translational N-myristoylation in humans.Nature communications · 2026Article
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Omadacycline - Associated Anticardiolipin Antibody Positivity and Hypercoagulable State: A Case Report and Review of Tetracycline - Induced Immune Dysregulation.Infection and drug resistance · 2026Article
- Doxycycline: An essential tool for Alzheimer's disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- T cell toxicity induced by tigecycline binding to the mitochondrial ribosome.Nature communications · 2025Article
- Mitochondrial ribosomal proteins: potential targets for cancer prognosis and therapy.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.
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