Desleucyl-Oritavancin with a Damaged D-Ala-D-Ala Binding Site Inhibits the Transpeptidation Step of Cell-Wall Biosynthesis in Whole Cells of Staphylococcus aureus
| Autor: | Sung Joon Kim, Shasad Sharif, Jacob Schaefer, Manmilan Singh |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus Peptidyl transferase 030106 microbiology Peptidoglycan medicine.disease_cause Biochemistry Article 03 medical and health sciences chemistry.chemical_compound Biosynthesis Isotopes In vivo Cell Wall Vancomycin medicine Binding site Binding Sites 030102 biochemistry & molecular biology Edman degradation biology Oritavancin Glycopeptides Lipoglycopeptides Dipeptides Fluorine Anti-Bacterial Agents chemistry Peptidyl Transferases biology.protein |
| Popis: | We have used solid-state nuclear magnetic resonance to characterize the exact nature of the dual mode of action of oritavancin in preventing cell-wall assembly in Staphylococcus aureus. Measurements performed on whole cells labeled selectively in vivo have established that des-N-methylleucyl-N-4-(4-fluorophenyl)benzyl-chloroeremomycin, an Edman degradation product of [19F]oritavancin, which has a damaged d-Ala-d-Ala binding aglycon, is a potent inhibitor of the transpeptidase activity of cell-wall biosynthesis. The desleucyl drug binds to partially cross-linked peptidoglycan by a cleft formed between the drug aglycon and its biphenyl hydrophobic side chain. This type of binding site is present in other oritavancin-like glycopeptides, which suggests that for these drugs a similar transpeptidase inhibition occurs. |
| Databáze: | OpenAIRE |
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