Allelic Variation in the Depressaria pastinacella CYP6AB3 Protein Enhances Metabolism of Plant Allelochemicals by Altering a Proximal Surface Residue and Potential Interactions with Cytochrome P450 Reductase

CYP6AB3v1, a cytochrome P450 monooxygenase in Depressaria pastinacella (parsnip webworm), is highly specialized for metabolizing imperatorin, a toxic furanocoumarin in the apiaceous host plants of this insect. Cloning and heterologous expression of CYP6AB3v2, an allelic variant identified in D. past...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-04, Vol.282 (14), p.10544-10552
Main Authors: Mao, Wenfu, Rupasinghe, Sanjeewa G., Zangerl, Arthur R., Berenbaum, May R., Schuler, Mary A.
Format: Article
Language:English
Subjects:
Alleles
Animals
Depressaria pastinacella
Electrons
Furocoumarins - chemistry
Furocoumarins - metabolism
Heracleum - chemistry
Insect Proteins - chemistry
Insect Proteins - genetics
Insect Proteins - metabolism
Moths - enzymology
Moths - genetics
Mutation, Missense
NADPH-Ferrihemoprotein Reductase - chemistry
NADPH-Ferrihemoprotein Reductase - genetics
NADPH-Ferrihemoprotein Reductase - metabolism
Pastinaca - chemistry
Quantitative Trait Loci - genetics
Substrate Specificity
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Summary:CYP6AB3v1, a cytochrome P450 monooxygenase in Depressaria pastinacella (parsnip webworm), is highly specialized for metabolizing imperatorin, a toxic furanocoumarin in the apiaceous host plants of this insect. Cloning and heterologous expression of CYP6AB3v2, an allelic variant identified in D. pastinacella, reveals that it metabolizes imperatorin at a rate (Vmax of 10.02 pmol/min/pmol of cytochrome P450 monooxygenase (P450)) significantly higher than CYP6AB3v1 (Vmax of 2.41 pmol/min/pmol) when supplemented with even low levels of cytochrome P450 reductase. Comparisons of the NADPH consumption rates for these variants indicate that CYP6AB3v2 utilizes this electron source at a faster rate than does CYP6AB3v1. Molecular modeling of the five amino acid differences between these variants and their potential interactions with P450 reductase suggests that replacement of Val92 on the proximal face of CYP6AB3v1 with Ala92 in CYP6AB3v2 affects interactions with P450 reductase so as to enhance its catalytic activity. Allelic variation at this locus potentially allows D. pastinacella to adapt to both intraspecific and interspecific variation in imperatorin concentrations in its host plants.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M607946200