Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally related to mammalian NK-lysin

The solution structure of bacteriocin AS-48, a 70-residue cyclic polypeptid e from Enterococcus faecalis. consists of a globular arrangement of five al pha-helices enclosing a compact hydrophobic core. The head-to-tail union li es in the middle of helix 5. a fact that is shown to have a pronounced effe ct on the stability of the three-dimensional structure. Positive charges in the side chains of residues in helix 4 and in the turn linking helix 4 to helix 5 form a cluster that most probably determine its antibacterial activ ity by promoting pore formation in cell membranes. A similar five-helix str uctural motif has been found in the antimicrobial NK-lysin. an effector pol ypeptide of T and natural killer (NK) cells. Bacteriocin AS-48 lacks the th ree disulfide bridges characteristic of the saposin fold present in NK-lysi n, and has no sequence homology with it. Nevertheless, the similar molecula r architecture and high positive charge strongly suggest a common mechanism of antibacterial action.