7s1h

Wild-type Escherichia coli ribosome with antibiotic linezolid

spinqualitylabelsall models 7s1h, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7s1h is a 10 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.35Å Ligands: 1MG, 2MA, 2MG, 3TD, 4D4, 5MC, 5MU, 6MZ, G7M, H2U, MG, OMC, OMG, OMU, PSU, ZLD, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RS20_ECOLI Binds directly to 16S ribosomal RNA.[HAMAP-Rule:MF_00500] Publication Abstract from PubMed 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. Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.,Tsai K, Stojkovic V, Lee DJ, Young ID, Szal T, Klepacki D, Vazquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG Nat Struct Mol Biol. 2022 Feb;29(2):162-171. doi: 10.1038/s41594-022-00723-9. , Epub 2022 Feb 14. PMID:35165456 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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