Glutathione-S-transferases

Glutathione-S-transferase
Enzyme classification
EC, category	2.5.1.18 ,  transferase
Response type	Aryl group transfer
Substrate	Glutathione, organic compounds
Products	Glutathione S conjugates

Glutathione S-transferases ( GSTs , also known as glutathione transferases ) are enzymes that catalyze the binding of glutathione to toxic metabolites or xenobiotics (organic compounds that are foreign to the organism) . The conjugates so formed can, depending on the organism, by transport out of the cell and excretion or by importing into vacuoles are removed and the following degradation of the metabolism. Glutathione transferases thus play a central role in the detoxification of organic substances.

The conjugation of glutathione usually takes place after activation of the substrate by oxidases , through a nucleophilic attack by the thiol group of the central cysteine of glutathione. Glutathione transferases have different substrate specificities and a large number of isoforms (e.g. 48 in Arabidopsis thaliana ) can detoxify a wide range of xenobiotics.

classification

For the following classes, the human genes are given at the end, where available:

• MAPEG ( microsomal GST-I): Homotrimeric membrane proteins that are highly conserved and occur in all living things, with lipoxygenase, and partly with leukotriene C4 synthase or glutathione peroxidase activity ( MGST1 , MGST2 , MGST3 )
• kappa : localized in mitochondria and peroxisomes ( GSTK1 )
• alpha : make up three percent of the soluble protein in the liver and are partially specialized in lipid peroxides ( GSTA1 , GSTA2 , GSTA3 , GSTA4 , GSTA5 ). mu : ( GSTM1 , GSTM2 , GSTM3 , GSTM4 , GSTM5 ). pi : ( GSTP1 ). alpha / mu / pi are mammal-specific
• sigma : also found in mammals , but more common in invertebrates ; DmGSTS1-1 makes up about one percent of the soluble protein in Drosophila melanogaster .
• theta : cannot utilize CDNB; Serine is catalytically active, in contrast to tyrosine at alpha / mu / pi ( GSTT1 , GSTT2 , GSTT4 see UniProt A8MPT4 )
• zeta : identical to maleylacetoacetate isomerase ( EC  5.2.1.2 ), catabolized α-halocarboxylic acids ( GSTZ1 )
• omega : in mammals, insects, worms; Cysteine ​​as the active center; similar to thioredoxin-like proteins show thiol transferase and dehydroascorbate reductase activity ( GSTO1 , GSTO2 , see glutathione transferase Omega )
• beta : bacterial enzymes with active cysteine, involved in the catabolism of organic molecules
• delta / epsilon : insect-specific with active serine; Function in case of resistance to secondary plant substances and insecticides
• helminthic GSTs

Use in biotechnology

Due to the high affinity of glutathione-S-transferases for glutathione, they are often used as protein tags in molecular biology . A fusion protein from the protein to be examined and a glutathione-S-transferase can be bound via a glutathione-containing matrix , which can be used in affinity chromatography to specifically enrich the fusion protein or factors that bind to the fusion protein ( pulldown assay ).

Individual evidence

1. ↑ Marrs, K .: The functions and regulation of glutathione S-transferases in plants . In: Annual Review of Plant Physiology and Plant Molecular Biology . No. 47, 1996, pp. 127-158.
2. ↑ Leustek, T., Martin, MN, Bick, J.-A., and Davies, JP: Pathways and Regulation of Sulfur Metabolism Revealed Through Molecular and Genetic Studies . In: Annual Review of Plant Physiology and Plant Molecular Biology . No. 51, 2000, pp. 141-165.
3. ↑ Yogesh C. Awasthi: Toxicology of Glutathione Transferases. CRC Press, 2006, ISBN 0-8493-2983-3 , pp. 15-19.