Journal article
Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach
Acta crystallographica. Section D, Biological crystallography., v 69(Pt 4), pp 520-533
Apr 2013
PMID: 23519660
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Using a carrier-protein strategy, the structure of teicoplanin bound to its bacterial cell-wall target has been determined. The structure reveals the molecular determinants of target recognition, flexibility in the antibiotic backbone and intrinsic radiation sensitivity of teicoplanin.
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.
Metrics
Details
- Title
- Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach
- Creators
- Nicoleta J Economou - Department of Biochemistry and Molecular BiologyIsaac J Zentner - Department of Biochemistry and Molecular BiologyEdwin Lazo - National Synchrotron Light SourceJean Jakoncic - National Synchrotron Light SourceVivian Stojanoff - National Synchrotron Light SourceStephen D Weeks - Department of Biochemistry and Molecular BiologyKimberly C Grasty - Department of Biochemistry and Molecular BiologySimon Cocklin - Department of Biochemistry and Molecular BiologyPatrick J Loll - Department of Biochemistry and Molecular Biology
- Publication Details
- Acta crystallographica. Section D, Biological crystallography., v 69(Pt 4), pp 520-533
- Publisher
- International Union of Crystallography
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000316743300004
- Scopus ID
- 2-s2.0-84875416420
- Other Identifier
- 991014878019504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods
- Biochemistry & Molecular Biology
- Biophysics
- Crystallography