GST dimers conjugate GSH with cytosolic substrates

Stable Identifier
Reaction [transition]
Homo sapiens
Glutathione conjugation of cytosolic substrates
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
The glutathione S-transferases (GSTs) catalyze the nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom. Their substrates include halogenonitrobenzenes, arene oxides, quinones, and alpha, beta-unsaturated carbonyls. Three major families of proteins are widely distributed in nature. Two of these, the cytosolic and mitochondrial GST, comprise soluble enzymes that are only distantly related whilst the third family comprises microsomal GST, referred to as membrane-associated proteins in eicosanoid and glutathione (MAPEG) metabolism.

At least 16 cytosolic GST subunits exist in human which are all in a dimeric form. Based on amino acid sequence similarities, seven classes of cytosolic GST are recognized in mammalian species; Alpha, Mu, Pi, Sigma, Theta, Omega, and Zeta (2–5). As well as being homodimers, the Alpha and Mu classes are also able to form heterodimers so a large number of isozymes are possible from all cytosolic GST subunits (Sinning et al. 1993, LeTrong et al. 2002, Ahmad et al. 1993, Pastore et al. 1998, Tars et al. 2010, Bruns et al. 1999, Balogh et al. 2010, Morel et al. 2002, Li et al. 2005, Patskovsky et al. 2006, Raghunathan et al. 1994, Patskovsky et al. 1999, Comstock et al. 1994, Board et al. 2000, Zhou et al. 2011, Zhou et al. 2012, Sun et al. 2011, Tars et al. 2006, Rossjohn et al. 1998, Polekhina et al. 2001, Inoue et al. 2003). Typical electrophilic substrates are chosen as examples for which the majority of the cytosolic GST isozymes act on.
Literature References
PubMed ID Title Journal Year
21668448 Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity

Regnier, F, Ghosh, S, Chang, KH, Sun, KH, Clawson, S, Mirzaei, H, Shah, K

J. Neurochem. 2011
11327815 Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity.

Blackburn, AC, Parker, MW, Polekhina, G, Board, PG

Biochemistry 2001
8182750 Crystal structure of human class mu glutathione transferase GSTM2-2. Effects of lattice packing on conformational heterogeneity

Rule, GS, Kretsinger, RH, Allison, TJ, Penington, CJ, Chandross, RJ, Raghunathan, S

J. Mol. Biol. 1994
20085333 Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal

Kripps, KA, Atkins, WM, Balogh, LM, Le Trong, I, Stenkamp, RE, Shireman, LM, Mannervik, B, Zhang, W

Biochemistry 2010
16081649 Thioredoxin-like domain of human kappa class glutathione transferase reveals sequence homology and structure similarity to the theta class enzyme

Ding, J, Xia, Z, Li, J

Protein Sci. 2005
10329152 Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products

Mannervik, B, Bruns, CM, Tainer, JA, Hubatsch, I, Ridderström, M

J. Mol. Biol. 1999
12627223 Mechanism of metal activation of human hematopoietic prostaglandin D synthase

Irikura, D, Kai, Y, Miyano, M, Matsumura, H, Urade, Y, Yamamoto, M, Kinugasa, S, Inoue, T, Okazaki, N, Uodome, N, Kumasaka, T

Nat Struct Biol 2003
20083122 Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases

Olin, B, Mannervik, B, Tars, K

J. Mol. Biol. 2010
10783391 Identification, characterization, and crystal structure of the Omega class glutathione transferases

Danley, DE, Rosner, MH, Schulte, GK, Hoth, LR, Perregaux, DE, Easteal, S, Chrunyk, BA, Griffor, MC, Geoghegan, KF, Gabel, CA, Pandit, J, Jermiin, LS, Chelvanayagam, G, Coggan, M, Kamath, AV, Board, PG

J Biol Chem 2000
8331657 Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes

Board, PG, Ji, X, Cowan, SW, Reinemer, P, Kleywegt, GJ, Armstrong, RN, Sinning, I, Dirr, HW, Gilliland, GL, Huber, R

J. Mol. Biol. 1993
10587441 An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases

Listowsky, I, Patskovsky, YV, Patskovska, LN

Biochemistry 1999
8431482 Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver

Singhal, SS, Ahmad, H, Saxena, M, Awasthi, YC

Biochim. Biophys. Acta 1993
22522127 Structural insights into the dehydroascorbate reductase activity of human omega-class glutathione transferases

Zhou, H, Brock, J, Oakley, AJ, Board, PG, Liu, D

J. Mol. Biol. 2012
16298388 Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant

Kleywegt, GJ, Olin, B, Shokeer, A, Mannervik, B, Tars, K, Larsson, AK

J. Mol. Biol. 2006
12042665 The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter

Coles, B, Le Ferrec, E, Rauch, C, Morel, F, Guillouzo, A

Pharmacogenetics 2002
8203914 A comparison of the enzymatic and physicochemical properties of human glutathione transferase M4-4 and three other human Mu class enzymes

Mannervik, B, Comstock, KE, Hao, XY, Widersten, M, Henner, WD

Arch. Biochem. Biophys. 1994
9839448 Purification and characterization of a novel alpha-class glutathione transferase from human liver

Petruzzelli, R, Lo Bello, M, Federici, G, Pastore, A, Ricci, G, Aureli, G, Di Ilio, C

Int. J. Biochem. Cell Biol. 1998
16548513 Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a

Patskovska, L, Listowsky, I, Almo, SC, Patskovsky, Y

Biochemistry 2006
12211029 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site

Atkins, WM, Le Trong, I, Stenkamp, RE, Adman, ET, Ibarra, C

Proteins 2002
21106529 Novel folding and stability defects cause a deficiency of human glutathione transferase omega 1

Zhou, H, Casarotto, MG, Brock, J, Board, PG, Oakley, AJ

J. Biol. Chem. 2011
9551553 Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site

Board, PG, Tan, KL, Parker, MW, Chelvanayagam, G, McKinstry, WJ, Verger, D, Oakley, AJ, Rossjohn, J, Flanagan, J

Structure 1998
Catalyst Activity

glutathione transferase activity of GST dimers [cytosol]

Orthologous Events
Cite Us!