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Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3- epi- deoxynivalenol

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


The molecular visualization of DON within F. graminearum Tri101 binding pocket. The C3 carbon (and attached -OH group) in DON (less-polar) is facing a non-polar amino acid (Leu16). In the case of 3-epi-DON (higher-polarity), the same group will be facing a matrix of non-polar (Leu16) and neutral (Trp380) amino acid residues.
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toxins-08-00261-f006: The molecular visualization of DON within F. graminearum Tri101 binding pocket. The C3 carbon (and attached -OH group) in DON (less-polar) is facing a non-polar amino acid (Leu16). In the case of 3-epi-DON (higher-polarity), the same group will be facing a matrix of non-polar (Leu16) and neutral (Trp380) amino acid residues.

Mentions: As mentioned in the Materials and Methods section, the FgTri101 enzyme crystal structure was solved by Garvey et al. [28] showing the key amino acids that occupy the active pocket of the enzyme. Among these amino acids are: Leu16, TRP380, SER378, SER379, and the catalytic His156 (Figure 6).


Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3- epi- deoxynivalenol
The molecular visualization of DON within F. graminearum Tri101 binding pocket. The C3 carbon (and attached -OH group) in DON (less-polar) is facing a non-polar amino acid (Leu16). In the case of 3-epi-DON (higher-polarity), the same group will be facing a matrix of non-polar (Leu16) and neutral (Trp380) amino acid residues.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037487&req=5

toxins-08-00261-f006: The molecular visualization of DON within F. graminearum Tri101 binding pocket. The C3 carbon (and attached -OH group) in DON (less-polar) is facing a non-polar amino acid (Leu16). In the case of 3-epi-DON (higher-polarity), the same group will be facing a matrix of non-polar (Leu16) and neutral (Trp380) amino acid residues.
Mentions: As mentioned in the Materials and Methods section, the FgTri101 enzyme crystal structure was solved by Garvey et al. [28] showing the key amino acids that occupy the active pocket of the enzyme. Among these amino acids are: Leu16, TRP380, SER378, SER379, and the catalytic His156 (Figure 6).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.