3VFJ

The structure of monodechloro-teicoplanin in complex with its ligand, using MBP as a ligand carrier

Summary for 3VFJ

• Entry DOI: 10.2210/pdb3vfj/pdb
• Related: 1JW4 3RUL 3RUM 3RUN 3VFK
• Related PRD ID: PRD_000882
• Descriptor: Maltose-binding periplasmic protein, C-terminal fused by Cys-Lys-D-Ala-D-Ala, MonodeChloro- Teicoplanin A2-2, ZINC ION, ... (10 entities in total)
• Functional Keywords: teicoplanin, acetylation of cyteine with iodoacetate modification, sugar binding protein-antibiotic complex, sugar binding protein/antibiotic
• Biological source: Escherichia coli; More
• Cellular location: Periplasm: P0AEX9
• Total number of polymer chains: 2
• Total formula weight: 44183.45

Authors

Economou, N.J.,Weeks, S.D.,Grasty, K.C.,Loll, P.J. (deposition date: 2012-01-09, release date: 2013-01-09, Last modification date: 2025-03-26)

Primary citation

Economou, N.J.,Zentner, I.J.,Lazo, E.,Jakoncic, J.,Stojanoff, V.,Weeks, S.D.,Grasty, K.C.,Cocklin, S.,Loll, P.J.
Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach.
Acta Crystallogr.,Sect.D, 69:520-533, 2013

PubMed 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.

PubMed: 23519660
DOI: 10.1107/S0907444912050469

Experimental method

X-RAY DIFFRACTION (2.05 Å)