7S1H
Wild-type Escherichia coli ribosome with antibiotic linezolid
This is a non-PDB format compatible entry.
Summary for 7S1H
| Entry DOI | 10.2210/pdb7s1h/pdb |
| EMDB information | 24800 24801 |
| Descriptor | 30S ribosomal protein S19, 23S rRNA, 5S rRNA, ... (56 entities in total) |
| Functional Keywords | escherichia coli ribosome, oxazolidinone, linezolid, ribosome-antibiotic complex, ribosome/antibiotic |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 52 |
| Total formula weight | 2144982.44 |
| Authors | Young, I.D.,Stojkovic, V.,Tsai, K.,Lee, D.J.,Fraser, J.S.,Galonic Fujimori, D. (deposition date: 2021-09-02, release date: 2021-11-17, Last modification date: 2023-11-15) |
| Primary citation | Tsai, K.,Stojkovic, V.,Lee, D.J.,Young, I.D.,Szal, T.,Klepacki, D.,Vazquez-Laslop, N.,Mankin, A.S.,Fraser, J.S.,Fujimori, D.G. Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics. Nat.Struct.Mol.Biol., 29:162-171, 2022 Cited by PubMed Abstract: The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. However, the molecular basis for context-specificity has not been elucidated. Here we show that the second-generation oxazolidinone radezolid also induces stalling with a penultimate alanine, and we determine high-resolution cryo-EM structures of linezolid- and radezolid-stalled ribosome complexes to explain their mechanism of action. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling due to repositioning of the modified nucleotide. Together, our findings provide molecular understanding for the context-specificity of oxazolidinones. PubMed: 35165456DOI: 10.1038/s41594-022-00723-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.35 Å) |
Structure validation
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