InterPro domain: IPR004045

In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing theirconjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of Cephalopoda is also a GST [ 1 , 2 , 3 , 4 ].

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family [ 5 , 6 ]. GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Soluble GSTs activate glutathione (GSH) to GS-. In many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulphur of GSH. These enzymes catalyse nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom [ 7 ].

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold, with each monomer composed of two distinct domains [ 8 ]. The N-terminal domain forms a thioredoxin-like fold that binds the glutathione moiety, while the C-terminal domain contains several hydrophobic alpha-helices that specifically bind hydrophobic substrates.

This entry represents the N-terminal domain of GST.

1. Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem. Res. Toxicol. 10, 2-18
2. Identification, characterization, and crystal structure of the Omega class glutathione transferases. J. Biol. Chem. 275, 24798-806
3. The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator. J. Biol. Chem. 276, 3319-23
4. Concise review of the glutathione S-transferases and their significance to toxicology. Toxicol. Sci. 49, 156-64
5. Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. Biochemistry 40, 1567-76
6. Bacterial glutathione S-transferases: what are they good for? J. Bacteriol. 179, 1431-41
7. Nomenclature for mammalian soluble glutathione transferases. Meth. Enzymol. 401, 1-8
8. 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site. Proteins 48, 618-27