The 18-amino acid cytolytic lipodepsipeptide tolaasin, produced in culture by virulent strains of Pseudomonas tolaasii, is the causal agent of brown blotch disease of the cultivated mushroom. Its N-terminal region bears a sequence of D-amino acids, then alternate L- and D-amino acids, and a 5-residue C-terminal lactone ring. The solution structure of tolaasin in sodium dodecyl sulfate (SDS) was studied by resorting to NMR spectroscopy and molecular dynamics simulations. In SDS tolaasin forms an amphipathic left-handed a-helix in the region DPro2-DThr14 comprising the sequence of seven D-amino acids and the L-D-L-D-D-region. To the best of our knowledge, this is the first recognized example of a left-handed a-helix that includes both D- and L-amino acids. The lactone loop adopts a boat-like conformation and is shifted from the helical axis as to form a golf-club overall conformation. These structural features will be of importance in understanding, and preventing, tolaasin role in the bacterial colonization of the host plant, and its toxic action on cells. Furthermore, the observed antimicrobial activity together with the potential resistance to enzymatic degradation and the increased antigenicity (both due to the presence of L- and D-amino acids into the a-helix) suggests for tolaasin a potential role as a therapeutic antibacterial peptide.
L- and D-amino acids form an amphipathic left-handed alpha-helix in the antibacterial lipodepsipeptide tolaasin
Amodeo P;MOTTA;
2003
Abstract
The 18-amino acid cytolytic lipodepsipeptide tolaasin, produced in culture by virulent strains of Pseudomonas tolaasii, is the causal agent of brown blotch disease of the cultivated mushroom. Its N-terminal region bears a sequence of D-amino acids, then alternate L- and D-amino acids, and a 5-residue C-terminal lactone ring. The solution structure of tolaasin in sodium dodecyl sulfate (SDS) was studied by resorting to NMR spectroscopy and molecular dynamics simulations. In SDS tolaasin forms an amphipathic left-handed a-helix in the region DPro2-DThr14 comprising the sequence of seven D-amino acids and the L-D-L-D-D-region. To the best of our knowledge, this is the first recognized example of a left-handed a-helix that includes both D- and L-amino acids. The lactone loop adopts a boat-like conformation and is shifted from the helical axis as to form a golf-club overall conformation. These structural features will be of importance in understanding, and preventing, tolaasin role in the bacterial colonization of the host plant, and its toxic action on cells. Furthermore, the observed antimicrobial activity together with the potential resistance to enzymatic degradation and the increased antigenicity (both due to the presence of L- and D-amino acids into the a-helix) suggests for tolaasin a potential role as a therapeutic antibacterial peptide.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
