Structure of ristocetin A in complex with a bacterial cell-wall mimetic

Antimicrobial drug resistance is a serious public health problem and the development of new antibiotics has become an important priority. Ristocetin A is a class III glycopeptide antibiotic that is used in the diagnosis of von Willebrand disease and which has served as a lead compound for the develo...

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Bibliographic Details
Published in:Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2009-08, Vol.65 (8), p.832-838
Main Authors: Nahoum, Virginie, Spector, Sherri, Loll, Patrick J.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - therapeutic use
antimicrobial resistance
Bacteria
Biomimetics - trends
Cell Wall - chemistry
Crystallization
Dimerization
Drug Design
glycopeptide antibiotics
Humans
Ligands
Methicillin Resistance
Methicillin-Resistant Staphylococcus aureus
Protein Binding
Protein Conformation
Research Papers
Ristocetin - chemistry
Ristocetin - metabolism
Ristocetin - therapeutic use
Staphylococcal Infections - drug therapy
vancomycin
Vancomycin - analogs & derivatives
Vancomycin - chemistry
Vancomycin - metabolism
Vancomycin - therapeutic use
X-Rays
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Summary:Antimicrobial drug resistance is a serious public health problem and the development of new antibiotics has become an important priority. Ristocetin A is a class III glycopeptide antibiotic that is used in the diagnosis of von Willebrand disease and which has served as a lead compound for the development of new antimicrobial therapeutics. The 1.0 Å resolution crystal structure of the complex between ristocetin A and a bacterial cell‐wall peptide has been determined. As is observed for most other glycopeptide antibiotics, it is shown that ristocetin A forms a back‐to‐back dimer containing concave binding pockets that recognize the cell‐wall peptide. A comparison of the structure of ristocetin A with those of class I glycopeptide antibiotics such as vancomycin and balhimycin identifies differences in the details of dimerization and ligand binding. The structure of the ligand‐binding site reveals a likely explanation for ristocetin A's unique anticooperativity between dimerization and ligand binding.
ISSN:1399-0047
0907-4449
1399-0047
DOI:10.1107/S0907444909018344