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. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD3CN/H2O and compare the structure with that in CD3OD and CDCl3. The conformations of VM1 in CD3CN/H2O, CD3OD and CDCl3 differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.
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Acknowledgements
J.D. and C.A.N. gratefully acknowledge receipt of financial support from La Trobe University. We thank LeRoy Lafferty (SDSU) for obtaining the 500 MHz NMR spectra.
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Dang, J., Metzger, R.P., Brownlee, R.T.C. et al. The conformational flexibility of the antibiotic virginiamycin M1. Eur Biophys J 34, 383–388 (2005). https://doi.org/10.1007/s00249-005-0464-1
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DOI: https://doi.org/10.1007/s00249-005-0464-1