Multiple roles for plant glutathione transferases in xenobiotic detoxification

Abstract

Discovered 40 years ago, plant glutathione transferases (GSTs) now have a well-established role in determining herbicide metabolism and selectivity in crops and weeds. Within the GST superfamily, the numerous and plant-specific phi (F) and tau (U) classes are largely responsible for catalyzing glutathione-dependent reactions with xenobiotics, notably conjugation leading to detoxification and, more rarely, bioactivating isomerizations. In total, the crystal structures of 10 plant GSTs have been solved and a highly conserved N-terminal glutathione binding domain and structurally diverse C-terminal hydrophobic domain identified, along with key coordinating residues. Unlike drug-detoxifying mammalian GSTs, plant enzymes utlilize a catalytic serine in place of a tyrosine residue. Both GSTFs and GSTUs undergo changes in structure during catalysis indicative of an induced fit mechanism on substrate binding, with an understanding of plant GST structure/function allowing these proteins to be engineered for novel functions in detoxification and ligand recognition. Several major crops produce alternative thiols, with GSTUs shown to use homoglutathione in preference to glutathione, in herbicide detoxification reactions in soybeans. Similarly, hydroxymethylglutathione is used, in addition to glutathione in detoxifying the herbicide fenoxaprop in wheat. Following GST action, plants are able to rapidly process glutathione conjugates by at least two distinct pathways, with the available evidence suggesting these function in an organ- and species-specific manner. Roles for GSTs in endogenous metabolism are less well defined, with the enzymes linked to a diverse range of functions, including signaling, counteracting oxidative stress, and detoxifying and transporting secondary metabolites.

Phytotoxic metabolites from Neofusicoccum parvum, a pathogen of Botryosphaeria dieback of grapevine

“…Thiols play a major role in maintaining the redox state of cells (homeostasis) and in the activity of an important part of enzymes that catalyse redox reactions, similarly to enzymes implicated in an antioxidant system. Two proteomicbased studies described the responses in woody tissues from fieldgrown grapevines (Magnin-Robert et al, 2014;Spagnolo et al, 2014b) and described the differential perturbations (at the protein and transcript levels) of the detoxification systems: glutathione-S-transferase (Cummins et al, 2011), peroxiredoxins (Tripathi et al, 2009), and epoxide hydrolase (Mowbray et al, 2006). These responses may indicate the presence and the activity of these toxins in woody tissues, leading to disruption of antioxidant systems.…”

Arabidopsis Glutathione Transferases U24 and U25 Exhibit a Range of Detoxification Activities with the Environmental Pollutant and Explosive, 2,4,6-Trinitrotoluene

“…The t and f class GSTs, have been most studied in cereal crops and weeds for their role in detoxifying agrichemicals. These GSTs have relatively high activities toward chloroacetanilide and triazine herbicides and other chlorinated xenobiotics (Cummins et al, 2011). While the ability to conjugate these synthetic compounds is not the endogenous role of t class GSTs, it is possible that these xenobiotics might share chemical similarities with endogenous substrates.…”

“…Plant cells contain flavoproteins capable of one-electron reduction activity, and the formation of reactive oxygen species from the one-electron reduction of TNT is likely to be a major cause of toxicity . Overexpression of plant GSTs has been shown to confer resistance to a number of biotic and abiotic stresses (Dixon and Edwards, 2010;Cummins et al, 2011), and it is possible that the GST-U24 and GST-U25 overexpression lines also have resistance to additional xenobiotics; members of the t class of GSTs are particularly associated with herbicide detoxification (Dixon and Edwards, 2010).…”

“…Glutathione transferases (GSTs) are a multigene family of proteins known to conjugate glutathione to electrophilic molecules and, in plants, are involved in the detoxification of herbicide xenobiotics (Cummins et al, 2011). Since GSTs have evolved the ability to catalyze glutathionelinked reactions with thousands of different chemical structures, it has been hypothesized that GSTs should play a central role, alongside glucosyltransferases, in the detoxification of TNT (Mezzari et al, 2005;Brentner et al, 2008).…”

“…Gene expression studies in poplar (Tanaka et al, 2007;Brentner et al, 2008) and Arabidopsis (Ekman et al, 2003;Mezzari et al, 2005;Gandia-Herrero et al, 2008) have identified GSTs up-regulated in response to TNT; however, to date, the biochemical response of GSTs toward TNT has not been investigated. The overexpression of plant GSTs has been shown to increase resistance to a range of stresses, with some t class GSTs shown to detoxify herbicides via a conjugation activity (Dixon and Edwards, 2010;Cummins et al, 2011). Many Arabidopsis GSTs (in common with some mammalian and other plant GSTs) exhibit a glutathione-dependent peroxide (GPOX) activity (Dixon and Edwards, 2010), catalyzing the reduction of lipid hydroperoxides to the respective monohydroxyalcohols, an activity that confers tolerance to a number of oxidative stresses (Dixon et al, 1998;Dixon and Edwards, 2010).…”