8AYE
E. coli 70S ribosome bound to thermorubin and fMet-tRNA
This is a non-PDB format compatible entry.
Summary for 8AYE
| Entry DOI | 10.2210/pdb8aye/pdb |
| EMDB information | 15712 |
| Descriptor | 50S ribosomal protein L33, 30S ribosomal protein S4, 30S ribosomal protein S5, ... (58 entities in total) |
| Functional Keywords | antibiotic, initiator trna, complex, macromolecule, ribosome |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 55 |
| Total formula weight | 2175376.72 |
| Authors | Sanyal, S.,Parajuli, N.P.,Emmerich, A.G. (deposition date: 2022-09-02, release date: 2023-03-01, Last modification date: 2025-03-12) |
| Primary citation | Parajuli, N.P.,Emmerich, A.,Mandava, C.S.,Pavlov, M.Y.,Sanyal, S. Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria. Nat Commun, 14:918-918, 2023 Cited by PubMed Abstract: Thermorubin (THB) is a long-known broad-spectrum ribosome-targeting antibiotic, but the molecular mechanism of its action was unclear. Here, our precise fast-kinetics assays in a reconstituted Escherichia coli translation system and 1.96 Å resolution cryo-EM structure of THB-bound 70S ribosome with mRNA and initiator tRNA, independently suggest that THB binding at the intersubunit bridge B2a near decoding center of the ribosome interferes with the binding of A-site substrates aminoacyl-tRNAs and class-I release factors, thereby inhibiting elongation and termination steps of bacterial translation. Furthermore, THB acts as an anti-dissociation agent that tethers the ribosomal subunits and blocks ribosome recycling, subsequently reducing the pool of active ribosomes. Our results show that THB does not inhibit translation initiation as proposed earlier and provide a complete mechanism of how THB perturbs bacterial protein synthesis. This in-depth characterization will hopefully spur efforts toward the design of THB analogs with improved solubility and effectivity against multidrug-resistant bacteria. PubMed: 36806263DOI: 10.1038/s41467-023-36528-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (1.96 Å) |
Structure validation
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