Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.
Feature 1:GSH binding site (G-site) [chemical binding site]
Evidence:
Structure:1EEM; Human omega class GST with bound GSH; contacts at 3.5A
Structure:1OYJ; Oryza sativa tau class GSTwith bound GSH; contacts at 3.5A
Structure:1F2E; Sphingomonas paucimobilis beta class GST with bound GSH; contacts at 3.5A
Comment:The GST active site is composed of a GSH binding site (G-site), common to all GSTs, and a xenobiotic binding site (H-site), which varies between different classes and isotypes. Residues from the N-terminal TRX-fold domain form the G-site while the H-site is comprised mainly of residues from the C-terminal alpha helical domain.
Jiyao W et al.(2023). "The conserved domain database in 2023.",