8B7Y
Cryo-EM structure of the E.coli 70S ribosome in complex with the antibiotic Myxovalargin B.
This is a non-PDB format compatible entry.
Summary for 8B7Y
| Entry DOI | 10.2210/pdb8b7y/pdb |
| Related | 7QQ3 |
| EMDB information | 14121 15905 |
| Related PRD ID | PRD_002441 |
| Descriptor | 23S ribosomal RNA, 50S ribosomal protein L16, 50S ribosomal protein L17, ... (57 entities in total) |
| Functional Keywords | ribosome, antibiotic, myxovalargin b, myxb, fmet-trna, p-trna |
| Biological source | Escherichia coli K-12 More |
| Total number of polymer chains | 52 |
| Total formula weight | 2126168.93 |
| Authors | Koller, T.O.,Graf, M.,Wilson, D.N. (deposition date: 2022-10-03, release date: 2023-01-25, Last modification date: 2023-02-01) |
| Primary citation | Koller, T.O.,Scheid, U.,Kosel, T.,Herrmann, J.,Krug, D.,Boshoff, H.I.M.,Beckert, B.,Evans, J.C.,Schlemmer, J.,Sloan, B.,Weiner, D.M.,Via, L.E.,Moosa, A.,Ioerger, T.R.,Graf, M.,Zinshteyn, B.,Abdelshahid, M.,Nguyen, F.,Arenz, S.,Gille, F.,Siebke, M.,Seedorf, T.,Plettenburg, O.,Green, R.,Warnke, A.L.,Ullrich, J.,Warrass, R.,Barry 3rd, C.E.,Warner, D.F.,Mizrahi, V.,Kirschning, A.,Wilson, D.N.,Muller, R. The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition. J.Am.Chem.Soc., 145:851-863, 2023 Cited by PubMed Abstract: Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against . To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent. PubMed: 36603206DOI: 10.1021/jacs.2c08816 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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