Current and future experimental strategies for structural analysis of trichothecene mycotoxins-a prospectus
Date
2011
Authors
Shank, Roxanne A.
Foroud, Nora Afsaneh
Hazendonk, Paul
Eudes, François
Blackwell, Barbara A.
Journal Title
Journal ISSN
Volume Title
Publisher
M D P I A G
Abstract
Fungal toxins, such as those produced by members of the order Hypocreales,
have widespread effects on cereal crops, resulting in yield losses and the potential for severe
disease and mortality in humans and livestock. Among the most toxic are the trichothecenes.
Trichothecenes have various detrimental effects on eukaryotic cells including an interference
with protein production and the disruption of nucleic acid synthesis. However, these toxins
can have a wide range of toxicity depending on the system. Major differences in the
phytotoxicity and cytotoxicity of these mycotoxins are observed for individual members of
the class, and variations in toxicity are observed among different species for each individual
compound. Furthermore, while diverse toxicological effects are observed throughout the
whole cellular system upon trichothecene exposure, the mechanism of toxicity is not well
understood. In order to comprehend how these toxins interact with the cell, we must first
have an advanced understanding of their structure and dynamics. The structural analysis
of trichothecenes was a subject of major interest in the 1980s, and primarily focused on
crystallographic and solution-state Nuclear Magnetic Resonance (NMR) spectroscopic
studies. Recent advances in structural determination through solution- and solid-state NMR,
as well as computation based molecular modeling is leading to a resurgent interest in the
structure of these and other mycotoxins, with the focus shifting in the direction of structural dynamics. The purpose of this work is to first provide a brief overview of the
structural data available on trichothecenes and a characterization of the methods commonly
employed to obtain such information. A summary of the current understanding of the
relationship between structure and known function of these compounds is also presented.
Finally, a prospectus on the application of new emerging structural methods on these and
other related systems is discussed.
Description
Open access
Keywords
Trichothecene , NMR , Solid-state NMR , Crystallography , NMR crystallography , Natural product , Mycotoxin , Structure , Structure-function , Molecular modeling , Molecular dynamics , Antibiotic , Ribosome
Citation
Shank, R.A., Foroud, N.A., Hazendonk, P., Eudes, F., & Blackwell, B.A. (2011). Current and future experimental strategies for structural analysis of trichothecene mycotoxins-a prospectus. Toxins, 3, 1518-1553. doi:10.3390/toxins3121518