title: 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.
authors.affiliation: Center for Bioactive Chemistry, Durham University, Durham, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Cummins
authors.forename: David P
authors.initials: DP
authors.lastname: Dixon
authors.forename: Stefanie
authors.initials: S
authors.lastname: Freitag-Pohl
authors.forename: Mark
authors.initials: M
authors.lastname: Skipsey
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
mesh_terms: D018556:Crops, Agricultural / Q000201:enzymology*; D005982:Glutathione Transferase / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D053209:Herbicide Resistance; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism*; D050217:Metabolic Detoxication, Phase II; D008958:Models, Molecular; D015394:Molecular Structure; D010802:Phylogeny; D057685:Plant Weeds / Q000201:enzymology*; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007306:Insecticides; D015262:Xenobiotics; D005982:Glutathione Transferase