Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3-epi-deoxynivalenol.
Deoxynivalenol (DON) is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON) in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC). In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding.
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON N1G5C9, Canada. yousef.hassan@agr.gc.ca.
Yousef I
YI
Hassan
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON N1G5C9, Canada. honghui.zhu@agr.gc.ca.
Honghui
H
Zhu
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON N1G5C9, Canada. yan.zhu@agr.gc.ca.
Yan
Y
Zhu
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON N1G5C9, Canada. ting.zhou@agr.gc.ca.
Ting
T
Zhou
D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D005670:Fusarium / Q000145:classification / Q000201:enzymology*; D008958:Models, Molecular; D010458:Peptidyl Transferases / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014255:Trichothecenes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D014255:Trichothecenes; D000123:Acetyltransferases; C110205:trichothecene 3-O-acetyltransferase; D010458:Peptidyl Transferases; C007262:deoxynivalenol
Tri101; deoxynivalenol; epimer; interactions; molecular; polarity