 |
PDBsum entry 3vfk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sugar binding protein/antibiotic
|
PDB id
|
|
|
|
3vfk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of the complex between teicoplanin and a bacterial cell-Wall peptide: use of a carrier-Protein approach.
|
|
|
Authors
|
|
N.J.Economou,
I.J.Zentner,
E.Lazo,
J.Jakoncic,
V.Stojanoff,
S.D.Weeks,
K.C.Grasty,
S.Cocklin,
P.J.Loll.
|
|
|
Ref.
|
|
Acta Crystallogr D Biol Crystallogr, 2013,
69,
520-533.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
