Molecular structure of a prostaglandin D synthase requiring glutathione from the brown planthopper, Nilaparvata lugens

Abstract

Prostaglandins are involved in many physiological processes, and prostaglandin synthases facilitate the detoxification of xenobiotics as well as endogenous compounds, such as through glutathione conjugation. Specifically, prostaglandin D synthase (PGDS) catalyzes the isomerization of PGH₂ to PGD₂. Here we report the identification and structural analysis of PGDS from the brown planthopper rice pest Nilaparvata lugens (nlPGDS), which belongs to the sigma-class glutathione transferases. The structure of nlPGDS in complex with glutathione was determined at a resolution of 2.0 Å by X-ray crystallography. Bound glutathione was localized to the glutathione-binding site (G-site). Enzyme activity measurements following site-directed mutagenesis of nlPGDS indicated that amino acid residues Tyr8, Leu14, Trp39, Lys43, Gln50, Val51, Gln63, and Ser64 in the G-site contribute to its catalytic activity. To our knowledge, this represents the first report of a PGDS in insects. Our findings provide insights into the mechanism of nlPGDS activity and potentially that of other insects and therefore may facilitate the development of more effective and safe insecticides.

Keywords: Enzyme specificity; GSH; Lepidoptera; Protein crystal structure.