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Structure of ristocetin A in complex with a bacterial cell-wall mimetic
Journal article   Open access

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

Virginie Nahoum, Sherri Spector and Patrick J Loll
Acta crystallographica. Section D, Biological crystallography., v 65(Pt 8), pp 832-838
01 Aug 2009
PMID: 19622867
url
https://doi.org/10.1107/S0907444909018344View
Published, Version of Record (VoR) Open

Abstract

glycopeptide antibiotics vancomycin Research Papers antimicrobial resistance
The crystal structure of the complex between ristocetin A and the cell-wall peptide mimetic N -acetyl-lysine- d -alanine- d -alanine has been solved. Structural details explaining the anticooperativity of the antibiotic have been identified. 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.

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Web of Science research areas
Biochemical Research Methods
Biochemistry & Molecular Biology
Biophysics
Crystallography
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