ArticleProceedings of the National Academy of Sciences of the United States of America2016
Inhibition of translation initiation complex formation by GE81112 unravels a 16S rRNA structural switch involved in P-site decoding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. 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.
- Article
- The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation.Nature communications · 2025Article
- An oligopeptide permease, OppABCD, requires an iron-sulfur cluster domain for functionality.Nature structural & molecular biology · 2024Article
- Natural Products That Contain Higher Homologated Amino Acids.Chembiochem : a European journal of chemical biology · 2024Review
- Full Profiling of GE81112A, an Underexplored Tetrapeptide Antibiotic with Activity against Gram-Negative Pathogens.Microbiology spectrum · 2023Article
- Total Synthesis of GE81112A: An Orthoester-Based Approach.The Journal of organic chemistry · 2023Article
- Article
- Oxidative modification of free-standing amino acids by Fe(II)/αKG-dependent oxygenases.Engineering microbiology · 2023Review
- Article
- Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores.Journal of the American Chemical Society · 2021Article
- Exploration of Iron- and a-Ketoglutarate-Dependent Dioxygenases as Practical Biocatalysts in Natural Product Synthesis.Synlett : accounts and rapid communications in synthetic organic chemistry · 2021Article
- Characterization of a Citrulline 4-Hydroxylase from Nonribosomal Peptide GE81112 Biosynthesis and Engineering of Its Substrate Specificity for the Chemoenzymatic Synthesis of Enduracididine.Angewandte Chemie (International ed. in English) · 2019Article
- Cold-Responsive Regions of Paradigm Cold-Shock and Non-Cold-Shock mRNAs Responsible for Cold Shock Translational Bias.International journal of molecular sciences · 2019Article
- Using the Bacterial Ribosome as a Discovery Platform for Peptide-Based Antibiotics.Biochemistry · 2019Review
- Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature.Nucleic acids research · 2018Article
- Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design.Annual review of biochemistry · 2018Review
- The Mechanisms of Action of Ribosome-Targeting Peptide Antibiotics.Frontiers in molecular biosciences · 2018Review
- Ribosomal selection of mRNAs with degenerate initiation triplets.Nucleic acids research · 2017Article
- RsgA couples the maturation state of the 30S ribosomal decoding center to activation of its GTPase pocket.Nucleic acids research · 2017Article
- Structure of a 30S pre-initiation complex stalled by GE81112 reveals structural parallels in bacterial and eukaryotic protein synthesis initiation pathways.Nucleic acids research · 2017Article
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12 authors.
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Abstract
In prokaryotic systems, the initiation phase of protein synthesis is governed by the presence of initiation factors that guide the transition of the small ribosomal subunit (30S) from an unlocked preinitiation complex (30S preIC) to a locked initiation complex (30SIC) upon the formation of a correct codon-anticodon interaction in the peptidyl (P) site. Biochemical and structural characterization of GE81112, a translational inhibitor specific for the initiation phase, indicates that the main mechanism of action of this antibiotic is to prevent P-site decoding by stabilizing the anticodon stem loop of the initiator tRNA in a distorted conformation. This distortion stalls initiation in the unlocked 30S preIC state characterized by tighter IF3 binding and a reduced association rate for the 50S subunit. At the structural level we observe that in the presence of GE81112 the h44/h45/h24a interface, which is part of the IF3 binding site and forms ribosomal intersubunit bridges, preferentially adopts a disengaged conformation. Accordingly, the findings reveal that the dynamic equilibrium between the disengaged and engaged conformations of the h44/h45/h24a interface regulates the progression of protein synthesis, acting as a molecular switch that senses and couples the 30S P-site decoding step of translation initiation to the transition from an unlocked preIC to a locked 30SIC state.
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