The still mysterious roles of cysteine-containing glutathione transferases in plants

Abstract

Glutathione transferases (GSTs) represent a widespread multigenic enzyme family able to modify a broad range of molecules. These notably include secondary metabolites and exogenous substrates often referred to as xenobiotics, usually for their detoxification, subsequent transport or export. To achieve this, these enzymes can bind non-substrate ligands (ligandin function) and/or catalyze the conjugation of glutathione onto the targeted molecules, the latter activity being exhibited by GSTs having a serine or a tyrosine as catalytic residues. Besides, other GST members possess a catalytic cysteine residue, a substitution that radically changes enzyme properties. Instead of promoting GSH-conjugation reactions, cysteine-containing GSTs (Cys-GSTs) are able to perform deglutathionylation reactions similarly to glutaredoxins but the targets are usually different since glutaredoxin substrates are mostly oxidized proteins and Cys-GST substrates are metabolites. The Cys-GSTs are found in most organisms and form several classes. While Beta and Omega GSTs and chloride intracellular channel proteins (CLICs) are not found in plants, these organisms possess microsomal ProstaGlandin E-Synthase type 2, glutathionyl hydroquinone reductases, Lambda, Iota and Hemerythrin GSTs and dehydroascorbate reductases (DHARs); the four last classes being restricted to the green lineage. In plants, whereas the role of DHARs is clearly associated to the reduction of dehydroascorbate to ascorbate, the physiological roles of other Cys-GSTs remain largely unknown. In this context, a genomic and phylogenetic analysis of Cys-GSTs in photosynthetic organisms provides an updated classification that is discussed in the light of the recent literature about the functional and structural properties of Cys-GSTs. Considering the antioxidant potencies of phenolic compounds and more generally of secondary metabolites, the connection of GSTs with secondary metabolism may be interesting from a pharmacological perspective.

Structure, function and evolution of the hemerythrin‐like domain superfamily

“…While most hemerythrin GSTs have a GST_N_3 (Pfam accession: PF13417) N ‐terminal domain, seven sequences in this group contain a structurally similar MetRS‐N fold (Pfam accession: PF09635). Hemerythrin GSTs may be involved in heavy metal‐detoxification processes in plants …”

CaM and CML emergence in the green lineage

“…The expanding list of sequenced genomes among the green lineage, from algae to cultivated crops, has facilitated comparative phylogenomics that can provide insight into the evolution and functional significance of protein families [32][33][34][35]. Land plants, such as angiosperms, gymnosperms, or bryophytes, originated from green algae, referred as charophytes, approximately 450 million year ago ( Figure 1) [36].…”

Trametes versicolor glutathione transferase Xi 3, a dual Cys‐GST with catalytic specificities of both Xi and Omega classes

“…deglutathionylation) [1]. Most GSTs that harbor a catalytic serine residue (Ser-GSTs) or a catalytic tyrosine residue (Tyr-GSTs) exhibit glutathione-transferase activity, and GSTs with a catalytic cysteine residue (Cys-GSTs) mainly possess glutathione-lyase activity (i.e.…”