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Originally published In Press as doi:10.1074/jbc.M607946200 on January 23, 2007

J. Biol. Chem., Vol. 282, Issue 14, 10544-10552, April 6, 2007
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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*Formula

Wenfu Mao{ddagger}, Sanjeewa G. Rupasinghe§, Arthur R. Zangerl{ddagger}, May R. Berenbaum{ddagger}, and Mary A. Schuler§1

From the Departments of {ddagger}Entomology and §Cell and Developmental Biology, University of Illinois, Urbana, Illinois 61801

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.


Received for publication, August 18, 2006 , and in revised form, January 5, 2007.

* This project was funded by National Science Foundation Grants DEB 0235773 and 0612376 (to M. R. B. and A. R. Z.) and National Institutes of Health Grant R01 GM071826 (to M. A. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental DNA sequence comparisons.

1 To whom correspondence should be addressed: Dept. of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 1201 W. Gregory Dr., 161 Edward R. Madigan Laboratory (ERML), Urbana, IL 61801. Tel.: 217-333-8784; Fax: 217-244-1336; E-mail: maryschu{at}uiuc.edu.


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