8g2a

Crystal structure of the A2503-C2,C8-dimethylated Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A-site Phe-tRNAphe, peptidyl P-site fMTHSMRC-tRNAmet, and deacylated E-site tRNAphe at 2.45A resolution

spinqualitylabelsall models 8g2a, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8g2a 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 2.45Å Ligands: 0TD, 2MG, 2MU, 4OC, 4SU, 5MC, 5MU, 8AH, 8AN, F3N, FME, G7M, K, M2G, MA6, MG, MIA, OMC, OMG, PSU, SF4, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL13_THET8 This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly (By similarity).[HAMAP-Rule:MF_01366] Publication Abstract from PubMed The bacterial ribosome is an essential drug target as many clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent resistance mechanisms to PTC-acting drugs in Gram-positive bacteria is C8-methylation of the universally conserved A2503 nucleobase by Cfr methylase in 23S ribosomal RNA. Despite its clinical importance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. Here, we report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-transfer RNAs. These structures reveal an allosteric rearrangement of nucleotide A2062 upon Cfr-mediated methylation of A2503 that likely contributes to the reduced potency of some PTC inhibitors. Additionally, we provide the structural bases behind two distinct mechanisms of engaging the Cfr-methylated ribosome by the antibiotics iboxamycin and tylosin. Structural basis of Cfr-mediated antimicrobial resistance and mechanisms to evade it.,Aleksandrova EV, Wu KJY, Tresco BIC, Syroegin EA, Killeavy EE, Balasanyants SM, Svetlov MS, Gregory ST, Atkinson GC, Myers AG, Polikanov YS Nat Chem Biol. 2024 Jul;20(7):867-876. doi: 10.1038/s41589-023-01525-w. Epub 2024 , Jan 18. PMID:38238495 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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