GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. GSTs are 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. 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. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.
Feature 1:GSH binding site (G-site) [chemical binding site]
Evidence:
Structure:1LJR; Human GST2-2 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.
Comment:The N-terminal serine is essential in activating the thiol group of GSH by stabilizing its thiolate anion form.
Jiyao W et al.(2023). "The conserved domain database in 2023.",