ArticleCell chemical biology2017
Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- An Alkaloid Biosynthetic Gene Bundle in Animals.Journal of the American Chemical Society · 2026Article
- Synthesis of Differentially Halogenated Lissoclimide Analogues To Probe Ribosome E-Site Binding.ACS chemical biology · 2025Article
- Exploring Marine Alkaloids: A Natural Approach to Cancer Treatment.Current pharmaceutical biotechnology · 2025Review
- TheMolecules (Basel, Switzerland) · 2023Article
- Orthogonally Protected Diaminocyclopentenones as Synthons: Total Synthesis of (±)-Agelastatin A.Organic letters · 2023Article
- Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction.JCI insight · 2023Article
- Using DMS-MaPseq to uncover the roles of DEAD-box proteins in ribosome assembly.Methods (San Diego, Calif.) · 2022Article
- Ataluren binds to multiple protein synthesis apparatus sites and competitively inhibits release factor-dependent termination.Nature communications · 2022Article
- Natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase.Acta pharmacologica Sinica · 2022Article
- Inhibition of the Eukaryotic 80S Ribosome as a Potential Anticancer Therapy: A Structural Perspective.Cancers · 2021Review
- Synthesis of Agelastatin A and Derivatives Premised on a Hidden Symmetry Element Leading to Analogs Displaying Anticancer Activity.Tetrahedron · 2021Article
- The Recurring Roles of Chlorine in Synthetic and Biological Studies of the Lissoclimides.Accounts of chemical research · 2021Review
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
- A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor.Biomolecules · 2020Article
- Article
- Understanding the role of intermolecular interactions between lissoclimides and the eukaryotic ribosome.Nucleic acids research · 2019Article
- High-Resolution Ribosome Profiling Defines Discrete Ribosome Elongation States and Translational Regulation during Cellular Stress.Molecular cell · 2019Article
- Assaying RNA structure with LASER-Seq.Nucleic acids research · 2019Article
- Tetracyclines Modify Translation by Targeting Key Human rRNA Substructures.Cell chemical biology · 2018Article
- Endogenous rRNA Sequence Variation Can Regulate Stress Response Gene Expression and Phenotype.Cell reports · 2018Article
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 3 countries.
Funding
Abstract
Protein synthesis plays an essential role in cell proliferation, differentiation, and survival. Inhibitors of eukaryotic translation have entered the clinic, establishing the translation machinery as a promising target for chemotherapy. A recently discovered, structurally unique marine sponge-derived brominated alkaloid, (-)-agelastatin A (AglA), possesses potent antitumor activity. Its underlying mechanism of action, however, has remained unknown. Using a systematic top-down approach, we show that AglA selectively inhibits protein synthesis. Using a high-throughput chemical footprinting method, we mapped the AglA-binding site to the ribosomal A site. A 3.5 Å crystal structure of the 80S eukaryotic ribosome from S. cerevisiae in complex with AglA was obtained, revealing multiple conformational changes of the nucleotide bases in the ribosome accompanying the binding of AglA. Together, these results have unraveled the mechanism of inhibition of eukaryotic translation by AglA at atomic level, paving the way for future structural modifications to develop AglA analogs into novel anticancer agents.
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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.