5WIS
Crystal structure of the Thermus thermophilus 70S ribosome in complex with methymycin and bound to mRNA and A-, P- and E-site tRNAs at 2.7A resolution
This is a non-PDB format compatible entry.
Summary for 5WIS
| Entry DOI | 10.2210/pdb5wis/pdb |
| Descriptor | 23S ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total) |
| Functional Keywords | macrolide, antibiotic, inhibitor, inhibition of translation, peptidyl transferase center, ribosome |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 112 |
| Total formula weight | 4572626.23 |
| Authors | Almutairi, M.M.,Svetlov, M.S.,Hansen, D.A.,Khabibullina, N.F.,Klepacki, D.,Kang, H.Y.,Sherman, D.H.,Vazquez-Laslop, N.,Polikanov, Y.S.,Mankin, A.S. (deposition date: 2017-07-20, release date: 2018-02-14, Last modification date: 2025-03-19) |
| Primary citation | Almutairi, M.M.,Svetlov, M.S.,Hansen, D.A.,Khabibullina, N.F.,Klepacki, D.,Kang, H.Y.,Sherman, D.H.,Vazquez-Laslop, N.,Polikanov, Y.S.,Mankin, A.S. Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins. Nucleic Acids Res., 45:9573-9582, 2017 Cited by PubMed Abstract: Antibiotics methymycin (MTM) and pikromycin (PKM), co-produced by Streptomyces venezuelae, represent minimalist macrolide protein synthesis inhibitors. Unlike other macrolides, which carry several side chains, a single desosamine sugar is attached to the macrolactone ring of MTM and PKM. In addition, the macrolactone scaffold of MTM is smaller than in other macrolides. The unusual structure of MTM and PKM and their simultaneous secretion by S. venezuelae bring about the possibility that two compounds would bind to distinct ribosomal sites. However, by combining genetic, biochemical and crystallographic studies, we demonstrate that MTM and PKM inhibit translation by binding to overlapping sites in the ribosomal exit tunnel. Strikingly, while MTM and PKM readily arrest the growth of bacteria, ∼40% of cellular proteins continue to be synthesized even at saturating concentrations of the drugs. Gel electrophoretic analysis shows that compared to other ribosomal antibiotics, MTM and PKM prevent synthesis of a smaller number of cellular polypeptides illustrating a unique mode of action of these antibiotics. PubMed: 28934499DOI: 10.1093/nar/gkx673 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.703 Å) |
Structure validation
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