Conformational properties of the macrocyclic trichothecene mycotoxin verrucarin A in solution

Abstract

Phase-sensitive nuclear Overhauser enhancement spectroscopy (NOESY) experiments, (3)J couplings and computational molecular modeling (MM2* and MMFF force fields) were employed to examine the conformational properties of verrucarin A in chloroform solutions. The MMFF force field calculations resulted in a family of 12 low-energy structures along with their populations, the latter being determined by the NMR analysis of molecular flexibility in solution(NAMFIS) deconvolution analysis. The concluded model was capable of reproducing successfully the experimental NOESY cross-peak volumes and the proton-coupling constants. Among the 12 conformers, the one which was similar to the structure of verrucarin A in the solid state was the predominant accounting for 75% of the total relative population, although other low-energy conformations contributed to a lesser degree in order to explain the experimental data.

Solvent and Water Mediated Structural Variations in Deoxynivalenol and Their Potential Implications on the Disruption of Ribosomal Function

“…Technological advances in structural determination have made it possible to perform more detailed structural analysis and dynamics. A small number of dynamic studies have been reported among the different classes of trichothecenes (Jarvis et al, 1990 ; Fragaki et al, 2008 ; Steinmetz et al, 2008 ; Chaudhary et al, 2011 ; Shank et al, 2011 ). Density functional theory (DFT) computations were carried out by Nagy et al ( 2005 ), on the internal dynamics of DON, which suggested that the lowest energy configuration contains an internal H-bonding network.…”

Current and Future Experimental Strategies for Structural Analysis of Trichothecene Mycotoxins—A Prospectus

“…Of note are the studies performed on DON by Nagy et al [xref137], verrucarin A by Fragaki et al ., and both verrucarin A and roridin A by Steinmetz et al . [138,139]. In all cases, molecular dynamics were employed to determine the relative conformations of the toxins in question, in order to better understand whether a single conformation is predominant, or whether multiple conformations exist simultaneously under physiological conditions.…”

“…MD simulations of these compounds were able to determine that in all likelihood DON exists in a single conformation which is entropically favored due to intramolecular hydrogen bonding interactions [137]. Verrucarin A predominantly exists in a single conformation which accounts for approximately 75% of the total relative population, while several other low-energy conformers account for the remaining population [138]; whereas, roridin A exists as a mixture of two nearly equi-energetic conformers [139]. …”

Natural sesquiterpenoids

“…99 NMR spectroscopy and computational molecular modelling have been used to examine the conformational properties of the macrolide ring in roridin A 100 and verrucarin A. 100,101 The 3-O-and 4-O-acetylation of trichothecenes by trichothecene 15-O-acetyl transferase encoded by Fusarium Tri3 have been investigated. 102 The effects on the trichothecene production in Fusarium sporotrichioides by treatment with the coumarin xanthotoxin have been studied.…”