8k2d

Cryo-EM structure of the yeast 80S ribosome with tigecycline, eEF2, Stm1 and eIF5A

spinqualitylabelsall models 8k2d, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8k2d is a 10 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Ligands: 5CT, GDP, MG, T1C, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RS26B_YEAST Publication Abstract from PubMed 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. Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.,Li X, Wang M, Denk T, Buschauer R, Li Y, Beckmann R, Cheng J Nat Commun. 2024 Jun 28;15(1):5481. doi: 10.1038/s41467-024-49797-7. PMID:38942792 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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