AI Article Synopsis
- The study used solid-state nuclear magnetic resonance to analyze how oritavancin prevents cell-wall assembly in Staphylococcus aureus.
- It was found that a modified version of oritavancin effectively inhibits the transpeptidase enzyme involved in cell-wall biosynthesis by binding to a specific site on the peptidoglycan.
- The binding mechanism identified for this drug may be similar in other glycopeptides like oritavancin, suggesting a common way they inhibit transpeptidase activity.
Article Abstract
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 [F]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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508972 | PMC |
| http://dx.doi.org/10.1021/acs.biochem.6b01125 | DOI Listing |
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