1.A.66 The Pardaxin (Pardaxin) Family
Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram-negative bacteria, is an important element against permeability of bactericidal agents, including antimicrobial peptides. Pardaxins (Pa1, Pa2, Pa3, and Pa4) comprise a group of pore-forming bactericidal peptides found in the mucous glands of sole fishes. They have shark-repellent and surfactant properties. Despite having a low net positive charge, pardaxins (possibly tetramers) contain a broad spectrum of antibacterial activities. Bhunia et al., (2010) reported the first three-dimensional structure of Pa4 bound to LPS micelles. The binding kinetics of Pa4 with LPS was estimated, and LPS/Pa4 interactions were characterized by a number of biophysical methods. In the LPS-Pa4 complex, Pa4 adopts a unique helix-turn-helix conformation resembling a 'horseshoe.' Interestingly, the LPS-bound structure of Pa4 shows striking differences from the structures determined in lipid micelles or organic solvents. Saturation transfer difference NMR identified residues of Pa4 that are intimately associated with LPS micelles. The results provide mechanistic insights into the outer membrane permeabilization by pardaxin.
Bactericidal pore-forming pardaxin (Pa4) permeabilized both lipid and lipopolysaccharide membranes. Five paralogues are known: Pa1, 2, 3, 4, and 5, all nearly identical to each other. The 3-d structure of Pa4 is known. It forms a helix-turn-helix conformation resembling a horseshoe (Bhunia et al., 2010).
Pardaxin of Pardachirus marmoratus (P81861)