Open AccessStructure of ristocetin A in complex with a bacterial cell‐wall mimetic
Author(s) -
Nahoum Virginie,
Spector Sherri,
Loll Patrick J.
Publication year - 2009
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444909018344
Subject(s) - ristocetin , glycopeptide , antibiotics , ligand (biochemistry) , chemistry , binding site , bacterial cell structure , peptide , cell wall , microbiology and biotechnology , biochemistry , biology , bacteria , immunology , von willebrand factor , receptor , genetics , platelet
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.