Back to Search
Start Over
The Ribosome-Binding Mode of Trichothecene Mycotoxins Rationalizes Their Structure-Activity Relationships.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Feb 05; Vol. 22 (4). Date of Electronic Publication: 2021 Feb 05. - Publication Year :
- 2021
-
Abstract
- Trichothecenes are the most prevalent mycotoxins contaminating cereal grains. Some of them are also considered as the virulence factors of Fusarium head blight disease. However, the mechanism behind the structure-activity relationship for trichothecenes remains unexplained. Filling this information gap is a crucial step for developing strategies to manage this large family of mycotoxins in food and feed. Here, we perform an in-depth re-examination of the existing structures of Saccharomyces cerevisiae ribosome complexed with three different trichothecenes. Multiple binding interactions between trichothecenes and 25S rRNA, including hydrogen bonds, nonpolar pi stacking interactions and metal ion coordination interactions, are identified as important binding determinants. These interactions are mainly contributed by the key structural elements to the toxicity of trichothecenes, including the oxygen in the 12,13-epoxide ring and a double bond between C <superscript>9</superscript> and C <superscript>10</superscript> . In addition, the C <superscript>3</superscript> -OH group also participates in binding. The comparison of three trichothecenes binding to the ribosome, along with their binding pocket architecture, suggests that the substitutions at different positions impact trichothecenes binding in two different patterns. Moreover, the binding of trichothecenes induced conformation changes of several nucleotide bases in 25S rRNA. This then provides a structural framework for understanding the structure-activity relationships apparent in trichothecenes. This study will facilitate the development of strategies aimed at detoxifying mycotoxins in food and feed and at improving the resistance of cereal crops to Fusarium fungal diseases.
- Subjects :
- Binding Sites
Edible Grain toxicity
Food Contamination
Fusarium chemistry
Fusarium pathogenicity
Inactivation, Metabolic
Models, Molecular
Molecular Structure
Mycotoxins metabolism
Mycotoxins toxicity
Nucleic Acid Conformation drug effects
RNA, Fungal chemistry
RNA, Fungal drug effects
RNA, Ribosomal chemistry
RNA, Ribosomal drug effects
Ribosomes drug effects
Ribosomes metabolism
Saccharomyces cerevisiae drug effects
Saccharomyces cerevisiae metabolism
Structure-Activity Relationship
Trichothecenes metabolism
Trichothecenes toxicity
Mycotoxins chemistry
Trichothecenes chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33562610
- Full Text :
- https://doi.org/10.3390/ijms22041604