Title: Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach
Authors: Economou, Nicoleta ×
Zentner, Isaac
Lazo, Edwin
Jakoncic, Jean
Stojanoff, Vivian
Weeks, Stephen
Grasty, Kimberly
Cocklin, Simon
Loll, Patrick #
Issue Date: Apr-2013
Publisher: Published for the International Union of Crystallography by Munksgaard
Series Title: Acta Crystallographica D, Biological Crystallography vol:69 issue:Pt 4 pages:520-533
Abstract: 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.
ISSN: 1399-0047
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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