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Publication Abstract from PubMed

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 A 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.

Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach.,Economou NJ, Zentner IJ, Lazo E, Jakoncic J, Stojanoff V, Weeks SD, Grasty KC, Cocklin S, Loll PJ Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):520-33. doi:, 10.1107/S0907444912050469. Epub 2013 Mar 14. PMID:23519660^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.