SFLDS00019

Glutathione Transferase (cytosolic)

SFLD entry
Member databaseSFLD
SFLD typefamily
Short nameGlutathione_Transferase_(cytos

Description

The cytosolic glutathione transferases (cytGSTs) are known for adding the tripeptide glutathione (GSH) to substrate compounds. The archetypal role of cytGSTs is in mammalian enzymatic detoxification, in which electrophilic small molecules are modified by the addition of GSH, making compounds more soluble. Glutathionylated compounds are recognized by transporters and exported from the cell. It is known that cytGSTs also catalyze other reactions like reduction of peroxides in which the glutathionylated compound is an intermediate. Certain bacteria use cytGSTs to exploit various compounds as a carbon source. All cytGSTs catalyze the nucleophilic attack of GSH on a substrate compound. The activation of GSH is achieved in part by interactions with a residue in the enzyme active site: a tyrosine ("AMPS" subgroup), or a serine or cysteine ("Main" subgroup). Cytosolic GSTs incorporate a distant variant of the thioredoxin fold. The great variation of reactions of the cytGSTs may be categorized into "reaction types" by similarities in chemistry. These reaction types range from nucleophilic substitution (SN2) and nucleophilic aromatic substitution (such as the well-known CDNB activity) to isomerization reactions.

A chart of the major cytGST reaction types with example reactions can be downloaded here: cytGST Reaction Types

A set of files with sequence and structure similarity networks that include representative network views (50% sequence identity filtered) that can be used as an overall visual guide to the superfamily, and that show where experimentally confirmed reaction types occur. This set of files can be downloaded here: Sequence and Structure Networks

A spreadsheet of cytGSTs that show which experimentally confirmed reaction types occur in representative nodes can be downloaded here:Reaction types in representative nodes

A detailed spreadsheet of cytGSTs in the full networks with experimentally confirmed evidence for GST-like reactions with reaction types, substrates, references, and nodes identifiers in the representative network can be downloaded here: Detailed reaction types and substrates

[5, 2, 1, 4, 3]
. CuratorNotes EFI

References

1.Evolution of a metabolic pathway for degradation of a toxic xenobiotic: the patchwork approach. Copley SD. Trends Biochem. Sci. 25, 261-5, (2000). View articlePMID: 10838562

2.Active site serine promotes stabilization of the reactive glutathione thiolate in rat glutathione transferase T2-2. Evidence against proposed sulfatase activity of the corresponding human enzyme. Jemth P, Mannervik B. J. Biol. Chem. 275, 8618-24, (2000). View articlePMID: 10722701

3.Large-scale determination of sequence, structure, and function relationships in cytosolic glutathione transferases across the biosphere. Mashiyama ST, Malabanan MM, Akiva E, Bhosle R, Branch MC, Hillerich B, Jagessar K, Kim J, Patskovsky Y, Seidel RD, Stead M, Toro R, Vetting MW, Almo SC, Armstrong RN, Babbitt PC. PLoS Biol. 12, e1001843, (2014). View articlePMID: 24756107

4.Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Sheehan D, Meade G, Foley VM, Dowd CA. Biochem. J. 360, 1-16, (2001). View articlePMID: 11695986

5.Structure, catalytic mechanism, and evolution of the glutathione transferases. Armstrong RN. Chem. Res. Toxicol. 10, 2-18, (1997). View articlePMID: 9074797

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