Characterization of a Drosophila glutathione transferase involved in isothiocyanate detoxification.

Glutathione transferases (GSTs) are ubiquitous key enzymes that catalyse the conjugation of glutathione to xenobiotic compounds in the detoxification process. GSTs have been proposed to play a dual role in the signal termination of insect chemodetection by modifying odorant and tasting molecules and by protecting the chemosensory system. Among the 40 GSTs identified in Drosophila melanogaster, the Delta and Epsilon groups are insect-specific. GSTs Delta and Epsilon may have evolved to serve in detoxification, and have been associated with insecticide resistance. Here, we report the heterologous expression and purification of the D. melanogaster GST Delta 2 (GSTD2). We investigated the capacity of GSTD2 to bind tasting molecules. Among them, we found that isothiocyanates (ITC), insecticidal compounds naturally present in cruciferous plant and perceived as bitter, are good substrates for GSTD2. The X-ray structure of GSTD2 was solved, showing the absence of the classical Ser catalytic residue, conserved in the Delta and Epsilon GSTs. Using molecular dynamics, the interaction of ITC with the GSTD2 three-dimensional structure is analysed and discussed. These findings allow us to consider a biological role for GSTD2 in chemoperception, considering GSTD2 expression in the chemosensory organs and the potential consequences of insect exposure to ITC.