6y69

Cryo-EM structure of an Escherichia coli 70S ribosome in complex with antibiotic TetracenomycinX

spinqualitylabelsall models 6y69, resolution 2.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.86Å Ligands: MG, OCW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel. This previously unappreciated binding site is located adjacent to the macrolide-binding site, where TcmX stacks on the noncanonical basepair formed by U1782 and U2586 of the 23S ribosomal RNA. Although the binding site is distinct from the macrolide antibiotics, our results indicate that like macrolides, TcmX allows translation of short oligopeptides before further translation is blocked. Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel.,Osterman IA, Wieland M, Maviza TP, Lashkevich KA, Lukianov DA, Komarova ES, Zakalyukina YV, Buschauer R, Shiriaev DI, Leyn SA, Zlamal JE, Biryukov MV, Skvortsov DA, Tashlitsky VN, Polshakov VI, Cheng J, Polikanov YS, Bogdanov AA, Osterman AL, Dmitriev SE, Beckmann R, Dontsova OA, Wilson DN, Sergiev PV Nat Chem Biol. 2020 Jun 29. pii: 10.1038/s41589-020-0578-x. doi:, 10.1038/s41589-020-0578-x. PMID:32601485 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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