6xhy | pdb_00006xhy

Crystal structure of the Thermus thermophilus 70S ribosome in complex with telithromycin, mRNA, aminoacylated A- and P-site tRNAs, and deacylated E-site tRNA at 2.60A resolution

spinqualitylabelsall models 6xhy, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6xhy is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: 0TD, 2MA, 2MG, 2MU, 31H, 4OC, 4SU, 5MC, 5MU, 7MG, F3N, K, M2G, MA6, MG, MIA, OMG, PSU, TEL, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 A resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance. Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance.,Svetlov MS, Syroegin EA, Aleksandrova EV, Atkinson GC, Gregory ST, Mankin AS, Polikanov YS Nat Chem Biol. 2021 Apr;17(4):412-420. doi: 10.1038/s41589-020-00715-0. Epub 2021 , Jan 18. PMID:33462493 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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