9QEH
Cryo-EM structure of the A2085-methylated 50S ribosome of a MLSb resistant S. aureus strain "MNY196" in complex with solithromycin
This is a non-PDB format compatible entry.
Summary for 9QEH
| Entry DOI | 10.2210/pdb9qeh/pdb |
| EMDB information | 53067 |
| Descriptor | Large ribosomal subunit protein bL33A, Large ribosomal subunit protein uL4, Large ribosomal subunit protein uL5, ... (36 entities in total) |
| Functional Keywords | ribosome |
| Biological source | Staphylococcus aureus subsp. aureus USA300 More |
| Total number of polymer chains | 31 |
| Total formula weight | 1383107.40 |
| Authors | Rivalta, A.,Yonath, A. (deposition date: 2025-03-10, release date: 2025-06-04, Last modification date: 2025-07-02) |
| Primary citation | Rivalta, A.,Fedorenko, A.,Le Scornet, A.,Thompson, S.,Halfon, Y.,Breiner Goldstein, E.,Cavdaroglu, S.,Melenitzky, T.,Hiregange, D.G.,Zimmerman, E.,Bashan, A.,Yap, M.F.,Yonath, A. Structural studies on ribosomes of differentially macrolide-resistant Staphylococcus aureus strains. Life Sci Alliance, 8:-, 2025 Cited by PubMed Abstract: Antimicrobial resistance is a major global health challenge, diminishing the efficacy of many antibiotics, including macrolides. In , an opportunistic pathogen, macrolide resistance is primarily mediated by Erm-family methyltransferases, which mono- or dimethylate A2058 in the 23S ribosomal RNA, reducing drug binding. Although macrolide-ribosome interactions have been characterized in nonpathogenic species, their structural basis in clinically relevant pathogens remains limited. In this study, we investigate the impact of -mediated resistance on drug binding by analyzing ribosomes from strains with varying levels of expression and activity. Using cryo-electron microscopy, we determined the high-resolution structures of solithromycin-bound ribosomes, including those with dimethylated A2058. Our structural analysis reveals the specific interactions that enable solithromycin binding despite double methylation and resistance, as corroborated by microbiological and biochemical data, suggesting that further optimization of ketolide-ribosome interactions could enhance macrolide efficacy against resistant strains. PubMed: 40490363DOI: 10.26508/lsa.202503325 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.08 Å) |
Structure validation
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