التفاصيل البيبلوغرافية
| العنوان: |
Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics |
| المؤلفون: |
Tsai, Kaitlyn, Stojković, Vanja, Lee, D John, Young, Iris D, Szal, Teresa, Klepacki, Dorota, Vázquez-Laslop, Nora, Mankin, Alexander S, Fraser, James S, Fujimori, Danica Galonić |
| المصدر: |
Nature Structural & Molecular Biology, vol 29, iss 2 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2022 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biochemistry and Cell Biology, Biological Sciences, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Alanine, Anti-Bacterial Agents, Binding Sites, Cryoelectron Microscopy, Linezolid, Models, Molecular, Oxazolidinones, Peptidyl Transferases, Protein Biosynthesis, RNA, Ribosomal, Transfer, Ribosomes, Chemical Sciences, Medical and Health Sciences, Biophysics, Developmental Biology, Biomedical and clinical sciences |
| جغرافية الموضوع: |
162 - 171 |
| الوصف: |
The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. However, the molecular basis for context-specificity has not been elucidated. Here we show that the second-generation oxazolidinone radezolid also induces stalling with a penultimate alanine, and we determine high-resolution cryo-EM structures of linezolid- and radezolid-stalled ribosome complexes to explain their mechanism of action. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling due to repositioning of the modified nucleotide. Together, our findings provide molecular understanding for the context-specificity of oxazolidinones. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt5dg246kc; https://escholarship.org/uc/item/5dg246kcTest |
| الإتاحة: |
https://escholarship.org/uc/item/5dg246kcTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.532FF352 |
| قاعدة البيانات: |
BASE |
