| Autor: |
Economou NJ; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA., Zentner IJ, Lazo E, Jakoncic J, Stojanoff V, Weeks SD, Grasty KC, Cocklin S, Loll PJ |
| Jazyk: |
angličtina |
| Zdroj: |
Acta crystallographica. Section D, Biological crystallography [Acta Crystallogr D Biol Crystallogr] 2013 Apr; Vol. 69 (Pt 4), pp. 520-33. Date of Electronic Publication: 2013 Mar 14. |
| DOI: |
10.1107/S0907444912050469 |
| Abstrakt: |
Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a D-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein-peptide-antibiotic complex. The 2.05 Å resolution MBP-peptide-teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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