Glutathione S-transferase
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The Glutathione S-transferase (GST) family of enzymes comprises a long list of cytosolic, mitochondrial, and microsomal proteins which are capable of multiple reactions with a multitude of substrates, both endogenous and xenobiotic.
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[edit] Families of GST
- Mammalian
- Alpha
- A1-1
- A2-2
- A3-3
- A4-4
- hGST5.8 (putative)
- Mu
- M1-1
- Pi
- P1-1
- Theta
- Zeta
- Omega
- Alpha
[edit] Structure of GSTs
Mammalian cytosolic GSTs are homodimeric, and the monomers are in the range of 22-29 kDa. They are active over a wide variety of substrates with considerable overlap.
[edit] Glutathione S-transferase and 'gene fusion'
Genetic engineers have used Glutathione S-transferase to create the so-called 'GST gene fusion system'. Here, GST is used to express, purify and detect proteins of interest. In a GST gene fusion system, the GST protein is incorporated into an expression vector alongside the gene sequence encoding the protein of interest. Induction of the vector results in expression of a fusion protein - the protein of interest fused to the GST protein, which can then be released from the cells and purified.
[edit] GSTs and Biotransformation
Glutathione S-transferases are considered, among several others, to contribute to the phase II biotransformation of xenobiotics. Drugs, poisons, and other compounds not traditionally listed in either groups are usually somewhat modified by the phase I and/or phase II mechanisms, and finally excreted from the body. GSTs contribute to this type of metabolism by conjugating these compounds (often electrophilic and somewhat lipophilic in nature) with reduced glutathione to facilitate dissolution in the aqueous cellular and extracelluar media, and from there, out of the body.
[edit] GST
The GST family comprise of numerous enzymes, which can constitute up to 10% of cytosolic protein in some mammalian organs (Boyer, 1989). GSTs catalyse the conjugation of reduced glutathione via the sulphydril group, to electrophilic centres on a wide variety of substrates (Douglas, 1987). This activity is useful in the detoxification of endogenous compounds such as peroxidised lipids (Leaver and George, 1998) as well as the metabolism of xenobiotics. Distribution The mammalian GST super-family is comprised of cytosolic dimeric isoenzymes of 45-55 kDa size which have been assigned to at least four generic classes: Alpha, Mu , Pi and Theta (Beckett and Hayes, 1992; Wilce and Parker, 1994). Most mammalian isoenzymes have activity for the substrate 1-chloro-2, 4-dinitrobenzene (CDNB), and spectrophotometric assays utilising this substrate are commonly used to report GST activity (Habig et al., 1974). GST was also used in SARS Coronavirus research by Ito et al.