Nisin is a natural peptide of lantibiotics group, which has antibacterial action against a wide range of Gram-positive bacteria. Nisin selectively binds to transmembrane carrier of peptidoglycan monomer units - lipid II. The conservative chemical structure of the binding site - pyrophosphate moiety of lipid II - makes nisin a promising prototype of new high-affine and selective antimicrobial agents, development of which is impossible without understanding of the exact mechanism of intermolecular recognition and interaction. In order to explore the structural-dynamic characteristics of nisin in water and lipid II in hydrated lipid bilayer, a series of molecular dynamics (MD) simulations of corresponding systems was carried out. It was shown that, being highly flexible in aqueous solution, the N-terminal part of nisin molecule adopts the major stable conformation in the presence of pyrophosphate. The latter one was found to manifest the unique arrangement of hydrogen bond acceptors in membrane-bound lipid II molecule. Among numerous lipid II conformations observed in the membrane, the only one is theoretically suitable for capturing by nisin. Thus, we suggest that the nisin/lipid II complex in bacterial membrane is formed via an induced fit mechanism involving the both partners.
lantibiotic, nisin, lipid II, biomembrane, molecular dynamics
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