Table of Contents
Journal of Crystallography
Volume 2016, Article ID 4504891, 6 pages
Research Article

The X-Ray Structure of the Ligand-Free Antibiotic Ristocetin-A Reveals the Role of the Monomer/Dimer Equilibrium in Its Binding Mode

Laboratoire de Cristallographie et RMN Biologiques, Faculté de Pharmacie, UMR 8015 CNRS, 4 avenue de l’Observatoire, 75006 Paris, France

Received 25 March 2016; Accepted 17 May 2016

Academic Editor: Rajesh G. Gonnade

Copyright © 2016 Thierry Prangé and William B. T. Cruse. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Ristocetin-A belongs to the group of the glycoheptapeptide antibiotics. The sulfate salt of ristocetin-A was crystallized in the P21 monoclinic space group with a homodimer in the asymmetric unit. The two subunits are linked back-to-back like the other members of the family via four peptide bonds forming a twisted β-sheet and exposing the binding pockets to the exterior. The two tetrasaccharide parts of this ligand-free antibiotic are in the anti/anti orientations contrary to what was found in the mono- and diliganded ristocetin-A/-(D-Ala-D-Ala) complexes in which the two tetrasaccharides of the dimer are syn/anti. The ligand-free dimer shows however some conformational differences between the two subunits, particularly in the terminal arabinose leading to one extended and one bent conformation of the tetrasaccharide moiety. Comparison between this structure and the two available mono- and diliganded structures confirms that the anti/anti to syn/anti flipping of the tetrasaccharide is a key step in the binding to the D-Ala-D-Ala-containing target sequence and cannot proceed without displacement of the monomer/dimer equilibrium.