InterPro domain: IPR040075

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. Cytosolic GSTs from mammals can be divided into four distinct classes: Alpha, Mu, Pi and Theta. 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 [ 1 , 2 ].

Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs [ 3 , 4 ]. 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 [ 5 , 6 ]. 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 [ 7 ].

This entry represents the N-terminal domain found in class Theta glutathione S-transferases (GSTs). Proteins containing this domain also include bacterial dichloromethane (DCM) dehalogenase.

1. Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and dihalomethanes. Chem. Res. Toxicol. 14, 1118-27
2. Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site. Structure 6, 309-22
3. Evidence for an essential serine residue in the active site of the Theta class glutathione transferases. Biochem. J. 311 ( Pt 1), 247-50
4. Mutagenesis of the active site of the human Theta-class glutathione transferase GSTT2-2: catalysis with different substrates involves different residues. Biochem. J. 319 ( Pt 1), 315-21
5. Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant. J. Mol. Biol. 355, 96-105
6. Residue 234 in glutathione transferase T1-1 plays a pivotal role in the catalytic activity and the selectivity against alternative substrates. Biochem. J. 388, 387-92
7. Purification and characterization of a recombinant human Theta-class glutathione transferase (GSTT2-2). Biochem. J. 315 ( Pt 3), 727-32