8K82
Cryo-EM structure of the yeast 80S ribosome with tigecycline, Not5 and P-site tRNA
This is a non-PDB format compatible entry.
Summary for 8K82
| Entry DOI | 10.2210/pdb8k82/pdb |
| EMDB information | 36945 |
| Descriptor | 18S rRNA, Small ribosomal subunit protein uS3, 40S ribosomal protein S4-A, ... (88 entities in total) |
| Functional Keywords | 80s ribosome, tigecycline, antibiotic, ribosome |
| Biological source | Saccharomyces cerevisiae More |
| Total number of polymer chains | 85 |
| Total formula weight | 3288578.86 |
| Authors | Buschauer, R.,Beckmann, R.,Cheng, J. (deposition date: 2023-07-28, release date: 2024-07-10, Last modification date: 2024-11-06) |
| Primary citation | Li, X.,Wang, M.,Denk, T.,Buschauer, R.,Li, Y.,Beckmann, R.,Cheng, J. Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline. Nat Commun, 15:5481-5481, 2024 Cited by PubMed Abstract: Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy. PubMed: 38942792DOI: 10.1038/s41467-024-49797-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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