Functional and Structural Diversity of Insect Glutathione S-transferases in Xenobiotic Adaptation

Abstract

As a superfamily of multifunctional enzymes that is mainly associated with xenobiotic adaptation, glutathione S-transferases (GSTs) facilitate insects' survival under chemical stresses in their environment. GSTs confer xenobiotic adaptation through direct metabolism or sequestration of xenobiotics, and/or indirectly by providing protection against oxidative stress induced by xenobiotic exposure. In this article, a comprehensive overview of current understanding on the versatile functions of insect GSTs in detoxifying chemical compounds is presented. The diverse structures of different classes of insect GSTs, specifically the spatial localization and composition of their amino acid residues constituted in their active sites are also summarized. Recent availability of whole genome sequences of numerous insect species, accompanied by RNA interference, X-ray crystallography, enzyme kinetics and site-directed mutagenesis techniques have significantly enhanced our understanding of functional and structural diversity of insect GSTs.

Keywords: enzyme; host adaptation; metabolic detoxification; oxidative stress; pesticide resistance.

Figure 1

Graphic representation of the xenobiotic adaptations in arthropods that have evolved through different mechanisms. The thickness of the blue arrows represents the concentration of xenobiotics.

Figure 2

Schematic illustrating the process of xenobiotic metabolism, which encompasses three phases I, II, III (Adopted from 137) as well as xenobiotic induced oxidative stress and molecular damage.

Figure 3

Structures of representative insect cytosolic GSTs. A. Ribbon diagram of Drosophila melanogaster dmGSTD1 (PDB: 3MAK). In subunit 1, the N-terminal domain I helices are shown in dark blue, and β-strands are shown in red, and the C-terminal domain II helices are shown in light blue. In subunit 2 the domain I helices are dark cyan β-strands are orange, and the domain II helices are light cyan. Glutathione is colored by the element and is shown in ball and stick format. B. Dimer (left) and monomer (right) ribbon diagrams of dmGSTD1 (PDB: 3MAK) overlayed with lipophilic surface representation. C. Secondary structure map of Anopheles dirus GSTD3-3 (PDB: 1JLV). Domain I helices are shown in dark blue and beta strands are shown in red. Domain II helices are shown in light blue. Loop regions for both domains I and II are shown in grey. The link region loop is dashed. Ribbon and surface diagrams were generated with UCSF ChimeraX.