8ud8

Crystal structure of the A2503-C2,C8-dimethylated Thermus thermophilus 70S ribosome in complex with cresomycin, mRNA, deacylated A-site tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.70A resolution

spinqualitylabelsall models 8ud8, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ud8 is a 22 chain structure with sequence from Escherichia coli, Escherichia virus T4 and 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, 2MG, 31H, 4OC, 4SU, 5MC, 5MU, 8AH, G7M, K, M2G, MA6, MG, MIA, OMC, OMG, OMU, PSU, UR3, WC9, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes evolutionarily diverse forms of antimicrobial resistance that render modern antibiotics ineffective. CRM exhibits in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We show that CRM is highly preorganized for ribosomal binding by determining its density functional theory-calculated, solution-state, solid-state, and (wild-type) ribosome-bound structures, which all align identically within the macrobicyclic subunits. Lastly, we report two additional x-ray crystal structures of CRM in complex with bacterial ribosomes separately modified by the ribosomal RNA methylases, chloramphenicol-florfenicol resistance (Cfr) and erythromycin-resistance ribosomal RNA methylase (Erm), revealing concessive adjustments by the target and antibiotic that permit CRM to maintain binding where other antibiotics fail. An antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance.,Wu KJY, Tresco BIC, Ramkissoon A, Aleksandrova EV, Syroegin EA, See DNY, Liow P, Dittemore GA, Yu M, Testolin G, Mitcheltree MJ, Liu RY, Svetlov MS, Polikanov YS, Myers AG Science. 2024 Feb 16;383(6684):721-726. doi: 10.1126/science.adk8013. Epub 2024 , Feb 15. PMID:38359125 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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