InterPro : IPR003080

Name  Glutathione S-transferase, alpha class Short Name  GST_alpha
Type  Family Description  Glutathione S-transferases (GSTs) are soluble proteins with typical molecular masses of around 50 kDa, each composed of two polypeptide subunits. GSTs catalyse the transfer of the tripeptide glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) to a co-substrate (R-X) containing a reactive electrophillic centre to form a polar S-glutathionylated reaction product (R-SG). Each soluble GST is a dimer of approximately 26 kDa subunits, typically forming a hydrophobic 50 kDa protein with an isoelectric point in the pH range 4-5. The ability to form heterodimers greatly increases the diversity of the GSTs, but the functional significance of this mixing and matching of subunits has yet to be determined. Each GST subunit of the protein dimer contains an independent catalytic site composed of two components. The first is a binding site specific for GSH or a closely related homologue (the G site) formed from a conserved group of amino-acid residues in the amino-terminal domain of the polypeptide. The second component is a site that binds the hydrophobic substrate (the H site), which is much more structurally variable and is formed from residues in the carboxy-terminal domain. Between the two domains is a short variable linker region of 5-10 residues. The GST proteins have evolved by gene duplication to perform a range of functional roles. GSTs also have non-catalytic roles, binding flavonoid natural products in the cytosol prior to their deposition in the vacuole. Recent studies have also implicated GSTs as components of ultraviolet-inducible cell signalling pathways and as potential regulators of apoptosis. The mammalian GSTs active in drug metabolism are now classified into the alpha, mu and pi classes. Additional classes of GSTs have been identified in animals that do not have major roles in drug metabolism; these include the sigma GSTs, which function as prostaglandin synthases. In cephalopods, however, sigma GSTs are lens S-crystallins, giving an indication of the functional diversity of these proteins. The soluble glutathione transferases can be divided into the phi, tau, theta, zeta and lambda classes. The theta and zeta GSTs have counterparts in animals, whereas the other classes are plant-specific. In the case of phi and tau GSTs, only subunits from the same class will dimerise. Within a class, however, the subunits can dimerise even if they are quite different in amino-acid sequence. An insect-specific delta class has also been described, and bacteria contain a prokaryote-specific beta class of GST. Alpha-class GSTs show substrate specificity for cumene hydroperoxide (CuOOH)and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-C1), amongst others. In addition, this class exhibits a number of differences from thecharacteristic GST structure: within domain II, there is a short 3-residuebeta-strand near the C-terminal segment and a longer alpha-7 helix (due toinsertions at the N terminus and near to the middle of this helix); domain Iis formed from two separate segments of the sequence. This occurs becausean extra helix (alpha-11) formed via folding of the C-terminal region of thepolypeptide chain is also part of this domain []. This helix covers the substrate bound in the H subsite, which is thought to explain the preference of alpha class GSTs for more hydrophobic compounds [].
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Sequence Features

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Proteins

InterPro protein domain ID --> Contigs

 

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2 Contains

Id Name Short Name Type
IPR004046 Glutathione S-transferase, C-terminal GST_C Domain
IPR004045 Glutathione S-transferase, N-terminal Glutathione_S-Trfase_N Domain

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2 Publications

First Author Title Year Journal Volume Pages
Dirr H X-ray crystal structures of cytosolic glutathione S-transferases. Implications for protein architecture, substrate recognition and catalytic function. 1994 Eur J Biochem 220 645-61
Allardyce CS The role of tyrosine-9 and the C-terminal helix in the catalytic mechanism of Alpha-class glutathione S-transferases. 1999 Biochem J 343 Pt 3 525-31



To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)