Keywords Parole chiave: Cethromycin, Erythromycin, Ketolide, Macrolide, Telithromycin, Antibiotic Resistance, Article, Bacterium Mutant, Binding Site, Crystal Structure, Deinococcus Radiodurans, Drug Mechanism, Drug Protein Binding, Drug Structure, Nonhuman, Priority Journal, Protein Domain, Protein Interaction, Ribosome, Anti-Bacterial Agents, Crystallization, Crystallography, X-Ray, Drug Resistance, Models, Molecular, Molecular Sequence Data, 23s, Bacteria (microorganisms), Posibacteria,
Affiliations Affiliazioni: *** IBB - CNR ***
Max-Planck-Res. U. Ribosomal Struct., Hamburg, Germany Max-Planck-Inst. for Molec. Genet., Berlin, Germany Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel Inst. of Biostructure and Bioimaging, CNR, Naples, Italy
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Brunger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Warren, G. L., Crystallography & NMR System: A new software suite for macromolecular structure determination (1998) Acta Crystallogr. D, 54, pp. 905-921
Goldman, R. C., Fesik, S. W., Doran, C. C., Role of protonated and neutral forms of macrolides in binding to ribosomes from gram-positive and gram-negative bacteria (1990) Antimicrob. Agents Chemother., 34, pp. 426-431
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Shain, C. S., Amsden, G. W., Telithromycin: The first of the ketolides (2002) Ann. Pharmacother., 36, pp. 452-464
Wallace, A. C., Laskowski, R. A., Thornton, J. M., LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions (1995) Protein Eng., 8, pp. 127-134
Structural insight into the antibiotic action of telithromycin against resistant mutants
The crystal structure of the ketolide telithromycin bound to the Deinococcus radiodurans large ribosomal subunit shows that telithromycin blocks the ribosomal exit tunnel and interacts with domains II and V of the 23S RNA. Comparisons to other clinically relevant macrolides provided structural insights into its enhanced activity against macrolide-resistant strains.
Structural insight into the antibiotic action of telithromycin against resistant mutants
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