Structure and dynamics of the antifungal molecules Syringotoxin-B and Syringopeptin-25A from molecular dynamics simulation.
The phytopathogen Pseudomonas syringae pv. syringae produces toxic cyclic lipodepsipeptides (CLPs): nona-peptides and syringopeptins. All CLPs inhibit the growth of many fungal species, including human pathogens, although different fungi display different degrees of sensitivity. The best studied CLPs are Syringomycin-E (SR-E), Syringotoxin-B (ST-B) and Syringopeptin-25A (SP-25A). Their biological activity is affected by membrane composition and their structural differences. We previously (Matyus et al. in Eur Biophys J 35:459-467, 2006) reported the molecular features and structural preferences of SR-E in water and octane environments. Here we investigate in atomic detail the molecular features of the two other main CLP components, ST-B and SP-25A, in water and octane by 200 ns molecular dynamics simulations (MD), using distance restraints derived from NMR NOE data (Ballio et al. in Eur J Biochem 234:747-758, 1995). We have obtained three-dimensional models of ST-B and SP-25A CLPs in different environments. These models can now be used as a basis to investigate the interactions of ST-B and SP-25A with lipid membranes an important further step towards a better understanding of the antifungal and antibacterial activity of these peptides.
Mátyus
E
E
Institute of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary. szedit@puskin.sote.hu
Blaskó
K
K
Fidy
J
J
Tieleman
D P
DP
D000935:Antifungal Agents / Q000494:pharmacology*; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D005656:Fungal Proteins / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D044224:Pseudomonas syringae / Q000378:metabolism*
D000935:Antifungal Agents; D005656:Fungal Proteins; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; D010456:Peptides, Cyclic; C098017:syringopeptin 25-A; C069036:syringotoxin B