The conformational flexibility of the antibiotic virginiamycin M 1

Abstract

The antibiotic virginiamycin is a combination of two molecules, virginiamycin M1 (VM1) and virginiamycin S1 (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl3 solution (Aust. J. Chem. 57:415, 2004; Org. Biomol. Chem. 2:2919, 2004) differs markedly from the conformation bound to a VM1 binding enzyme (Sugantino and Roderick in Biochemistry 41:2209, 2002) and to 50S ribosomes (Hansen et al. in J. Mol. Biol. 330:1061, 2003) as found by X-ray crystallographic studies...