3VFJ: The Structure of Monodechloro-teicoplanin in Complex With ITS Ligand, Using MBP as a Ligand Carrier

Citation:
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 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.
PDB ID: 3VFJDownload
MMDB ID: 106468
PDB Deposition Date: 2012/1/9
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
Similar Structures:
Biological Unit for 3VFJ: dimeric; determined by author and by software (PISA)
Molecular Components in 3VFJ
Label Count Molecule
Protein (1 molecule)
1
Maltose-binding Periplasmic Protein, C-terminal Fused by Cys-lys-d-ala-d-ala(Gene symbol: malE)
Molecule annotation
Nucleotide(1 molecule)
1
Monodechloro- Teicoplanin A2-2
Molecule annotation
Chemicals (16 molecules)
1
8
2
2
3
2
4
1
5
1
6
1
7
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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