6XHW
Crystal structure of the A2058-unmethylated Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A- and P-site tRNAs, and deacylated E-site tRNA at 2.50A resolution
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Summary for 6XHW
| Entry DOI | 10.2210/pdb6xhw/pdb |
| Descriptor | 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total) |
| Functional Keywords | macrolide, antibiotic, resistance, methylation, a2058, 23s rrna, 70s ribosome, inhibition of translation, peptidyl transferase center, nascent peptide exit tunnel, ribosome |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 112 |
| Total formula weight | 4571007.67 |
| Authors | Svetlov, M.S.,Syroegin, E.A.,Aleksandrova, E.V.,Atkinson, G.C.,Gregory, S.T.,Mankin, A.S.,Polikanov, Y.S. (deposition date: 2020-06-19, release date: 2020-12-23, Last modification date: 2023-11-15) |
| Primary citation | Svetlov, M.S.,Syroegin, E.A.,Aleksandrova, E.V.,Atkinson, G.C.,Gregory, S.T.,Mankin, A.S.,Polikanov, Y.S. Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nat.Chem.Biol., 17:412-420, 2021 Cited by PubMed Abstract: Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 Å resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance. PubMed: 33462493DOI: 10.1038/s41589-020-00715-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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