Proceedings of the National Academy of Sciences - PNAS, 2008-09, Vol.105 (36), p.13339-13344
2008
Details
- Autor(en) / Beteiligte
- Titel
- oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2008-09, Vol.105 (36), p.13339-13344
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2008
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The oxazolidinones represent the first new class of antibiotics to enter into clinical usage within the past 30 years, but their binding site and mechanism of action has not been fully characterized. We have determined the crystal structure of the oxazolidinone linezolid bound to the Deinococcus radiodurans 50S ribosomal subunit. Linezolid binds in the A site pocket at the peptidyltransferase center of the ribosome overlapping the aminoacyl moiety of an A-site bound tRNA as well as many clinically important antibiotics. Binding of linezolid stabilizes a distinct conformation of the universally conserved 23S rRNA nucleotide U2585 that would be nonproductive for peptide bond formation. In conjunction with available biochemical data, we present a model whereby oxazolidinones impart their inhibitory effect by perturbing the correct positioning of tRNAs on the ribosome.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0804276105Titel-ID: cdi_pnas_primary_105_36_13339
- Format
- –
- Schlagworte
- Anti-Bacterial Agents - chemistry, Anti-Bacterial Agents - pharmacology, Antibiotics, Bacteria, Binding Sites, Biochemistry, Biological Sciences, Crystal structure, Deinococcus - drug effects, Deinococcus - enzymology, Deinococcus radiodurans, Drug interactions, Genetic mutation, Models, Molecular, Nucleic Acid Conformation, Nucleotides, Oxazolidinones, Oxazolidinones - chemistry, Oxazolidinones - pharmacology, Peptidyl Transferases - chemistry, Peptidyl Transferases - metabolism, Protein Binding, Protein Structure, Tertiary, Protein synthesis, Ribosomes, Ribosomes - drug effects, Ribosomes - enzymology, RNA, Transfer - chemistry, RNA, Transfer - metabolism, Transfer RNA