InterPro domain: IPR034330
General Information
- Identifier IPR034330
- Description Glutathione S-transferases, class Zeta , C-terminal
- Number of genes 190
- Gene duplication stats Loading...
Abstract
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 thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain [ 1 , 2 ].
Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor [ 3 , 4 ]. They show little GSH-conjugating activity towards traditional GST substrates, but display modest GSH peroxidase activity [ 5 ]. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid [ 6 ].
This entry represents the C-terminal domain of the glutathione S-transferase (GST) class Zeta subfamily members.
1. Analysis of the glutathione S-transferase (GST) gene family. Hum. Genomics 1, 460-4
2. Organisation and structural evolution of the rice glutathione S-transferase gene family. Mol. Genet. Genomics 271, 511-21
3. Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism. Mol. Cell. Biol. 22, 4943-51
4. The structure of a zeta class glutathione S-transferase from Arabidopsis thaliana: characterisation of a GST with novel active-site architecture and a putative role in tyrosine catabolism. J. Mol. Biol. 308, 949-62
5. Zeta, a novel class of glutathione transferases in a range of species from plants to humans. Biochem. J. 328 ( Pt 3), 929-35
6. Glutathione transferase zeta-catalyzed biotransformation of dichloroacetic acid and other alpha-haloacids. Chem. Res. Toxicol. 11, 1332-8