Nisin is the first discovered lantibiotics and to date its antibacterial mechanism has been investigated using a variety of methods. While the structure of nisin/lipid-II complex in solution is established, the native structure of the complex in lipid bilayer is unknown. In order to predict the complex structure in membrane, we conducted a series of molecular dynamics simulations of isolated molecules in their natural environment and their complex in solution. Our experiments revealed that the membrane-bound lipid-II could adopt conformations theoretically suitable for capturing by the "trap" (nisin). By contrast, free nisin molecule does not correspond to those found in complex structures, however, it high flexibility suggests that target capture leads to induced structural changes. Furthermore, it was shown, that lipid-II forms stable changes of membrane surface topography and it hydrophobic properties. Thus, we suggest that lipid-II with its membrane surrounding forms a specific platform that is recognized by lantibiotics as the binding site.
lantibiotics, nisin, lipid-II, molecular dynamics
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