Structure and dynamics of the antifungal molecules Syringotoxin-B and Syringopeptin-25A from molecular dynamics simulation

Abstract

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.

Biosurfactants produced by Pseudomonas syringae pv tabaci: A versatile mixture with interesting emulsifying properties

“…These findings provided information about the hydrophilic character of these molecules [14]. Different properties such as chemical structure, critical micellar concentration and antimicrobial activity have been studied for other P. syringae metabolites such as syringopeptins, syringomicins, corpetin and arthrofactin [15][16][17].…”

Channel-forming activity of syringopeptin 25A in mercury-supported phospholipid monolayers and negatively charged bilayers

“…NMR investigations in aqueous solution showed that SP25A assumes a conformation having distinct structural portions, e.g. a loop region (amino acids 2-6), a left-handed helical region (amino acids [8][9][10][11][12][13][14][15], and an octadepsipeptide moiety (amino acids [18][19][20][21][22][23][24][25] that resembles the seam of a tennis ball [3,4]. Syringopeptins have phytotoxic, antifungal and antibacterial properties.…”

Molecular dynamics investigation of cyclic natriuretic peptides: Dynamic properties reflect peptide activity

“…Molecular dynamics (MD) simulations have been demonstrated to be a suitable technique to evaluate conformational ensemble of disordered peptides which consists of a variety of conformations [28][29][30][31]. In the this contribution, we present a molecular dynamics (MD) investigation of NPs in solution starting from their structure bound to the NPR-C [21,23] with the aim of providing a high-resolution atomistic view of their conformational ensemble in solution and of specific interactions that cannot be easily captured by experimental techniques [32][33][34].…”