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

✍ Scribed by Nahoum, Virginie ;Spector, Sherri ;Loll, Patrick J.

• Publisher: International Union of Crystallography
• Year: 2009
• Tongue: English
• Weight: 606 KB
• Volume: 65
• Category: Article
• ISSN: 0907-4449
• DOI: 10.1107/s0907444909018344

✦ Synopsis

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 A 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.