Canadian Forest Service Publications

Structural features conferring dual Geranyl/Farnesyl diphosphate synthase activity to an aphid prenyltransferase. 2009. Vandermoten, S.; Santini, S.; Haubruge, E.; Heuze, F.; Francis, F.; Brasseur, R.; Cusson, M.; Charloteaux, B. Insect Biochem. Mol. Biol. 39: 707-716.

Year: 2009

Issued by: Laurentian Forestry Centre

Catalog ID: 30291

Language: English

Availability: PDF (request by e-mail)

Available from the Journal's Web site.
DOI: 10.1016/j.ibmb.2009.08.007

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In addition to providing lipid chains for protein prenylation, short-chain isoprenyl diphosphate synthases (scIPPSs) play a pivotal role in the biosynthesis of numerous mevalonate pathway end-products, including insect juvenile hormone and terpenoid pheromones. For this reason, they are being considered as targets for pesticide development. Recently, we characterized an aphid scIPPS displaying dual geranyl diphosphate (GPP; C10)/farnesyl diphosphate (FPP; C15) synthase activity in vitro. To identify the mechanism(s) responsible for this dual activity, we assessed the product selectivity of aphid scIPPSs bearing mutations at Gln107 and/or Leu110, the fourth and first residue upstream from the "first aspartate-rich motif" (FARM), respectively. All but one resulted in significant changes in product chain-length selectivity, effectively increasing the production of either GPP (Q107E, L110W) or FPP (Q107F, Q107F–L110A); the other mutation (L110A) abolished activity. Although some of these effects could be attributed to changes in steric hindrance within the catalytic cavity, molecular dynamics simulations identified other contributing factors, including residue-ligand Van der Waals interactions and the formation of hydrogen bonds or salt bridges between Gln107 and other residues across the catalytic cavity, which constitutes a novel product chain-length determination mechanism for scIPPSs. Thus the aphid enzyme apparently evolved to maintain the capacity to produce both GPP and FPP through a balance between these mechanisms.