1233335-10-8Relevant academic research and scientific papers
Crystal structures of two vancomycin complexes with phosphate and N-AcetylD-Ala. structural comparison between low-affinity and high-affinity ligand complexes of vancomycin
Kikuchi, Takanori,Karki, Shyam,Fujisawa, Ikuhide,Matsushima, Yoshitaka,Nitanai, Yasushi,Aoki, Katsuyuki
, p. 391 - 400 (2010)
Crystal structures of two vancomycin complexes with phosphate and N-acetylD-Ala (AcDA) were determined. Each complex involves two crystallographically independent vancomycin molecules (V1 and V2) in the asymmetric unit, which form a usually observed back-to-back arranged vancomycin dimer V1V2 with two disaccharide chains packed in a head-to-head manner, but only one of the two ligand-binding sites is occupied. Comparison of the published crystal structures of low-affinity (small in molecular size) ligand complexes of vancomycin with high-affinity (large) ligand complexes reveals that when the high-affinity ligand binds, three structural factors (hydrogen-bonding interactions between the two peptide-backbones and hydrophobic intra-dimer sugarring and ring (face)ring (edge) interactions) work to enhance the stabilization of the back-to-back dimer-interface, an important factor that is believed to promote antibacterial activity. It has also been revealed, by examining the high-affinity ligand complexes (including N-acetylDAlaD-Ala), that sugarligand interaction could cause different affinities of the two halves of the dimer; this is a factor responsible for the failure of the ligand binding to V1 in the AcDA complex. Possible scenarios for the formation of vancomycin complexes with low-affinity as well as high-affinity ligands are presented.
