6OM6
Structure of trans-translation inhibitor bound to E. coli 70S ribosome with P site tRNA
This is a non-PDB format compatible entry.
Summary for 6OM6
| Entry DOI | 10.2210/pdb6om6/pdb |
| EMDB information | 20121 |
| Descriptor | 23S ribosomal RNA, 50S ribosomal protein L6, 50S ribosomal protein L9, ... (55 entities in total) |
| Functional Keywords | trans-translation, translation, antibiotic, ribosome |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 54 |
| Total formula weight | 2164378.90 |
| Authors | Hoffer, E.D.,Mehrani, A.,Keiler, K.C.,Stagg, S.M.,Dunham, C.M. (deposition date: 2019-04-18, release date: 2021-02-10, Last modification date: 2025-03-19) |
| Primary citation | Aron, Z.D.,Mehrani, A.,Hoffer, E.D.,Connolly, K.L.,Srinivas, P.,Torhan, M.C.,Alumasa, J.N.,Cabrera, M.,Hosangadi, D.,Barbor, J.S.,Cardinale, S.C.,Kwasny, S.M.,Morin, L.R.,Butler, M.M.,Opperman, T.J.,Bowlin, T.L.,Jerse, A.,Stagg, S.M.,Dunham, C.M.,Keiler, K.C. trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo. Nat Commun, 12:1799-1799, 2021 Cited by PubMed Abstract: Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways. PubMed: 33741965DOI: 10.1038/s41467-021-22012-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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