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. pastinacella, reveals that it metabolizes imperatorin at a rate (V(max) of 10.02 pmol/min/pmol of cytochrome P450 monooxygenase (P450)) significantly higher than CYP6AB3v1 (V(max) 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 Val(92) on the proximal face of CYP6AB3v1 with Ala(92) 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.
Mao
Wenfu
W
Departments of Entomology and Cell and Developmental Biology, University of Illinois, Urbana, Illinois 61801, USA.
Rupasinghe
Sanjeewa G
SG
Zangerl
Arthur R
AR
Berenbaum
May R
MR
Schuler
Mary A
MA
D000483:Alleles; D000818:Animals; D004583:Electrons; D011564:Furocoumarins / Q000737:chemistry / Q000378:metabolism*; D030002:Heracleum / Q000737:chemistry; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009036:Moths / Q000201:enzymology* / Q000235:genetics; D020125:Mutation, Missense; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028529:Pastinaca / Q000737:chemistry; D040641:Quantitative Trait Loci / Q000235:genetics; D013379:Substrate Specificity
D011564:Furocoumarins; D019476:Insect Proteins; D009251:NADPH-Ferrihemoprotein Reductase; C031534:imperatorin