PROSITE documentation PDOC50404Soluble glutathione S-transferase N- and C-terminal domain profiles
Glutathione S-transferases (GSTs) (EC 2.5.1.18) are involved in detoxification of xenobiotic compounds and in the biosynthesis of important metabolites. Two distinct superfamilies of GST isoenzymes exist. The larger superfamily comprises cytosolic, or soluble, dimeric enzymes that are principally, but not exclusively, involved in biotransformation of toxic xenobiotics and endobiotics. The other superfamily is composed of microsomal proteins primarily involved in arachidonic acid metabolism. The microsomal GSTs, grouped together as a separate entity, are collectively called MAPEG, designating membrane-associated proteins in eicosanoid and glutathione metabolism (see <PDOC00999>) [1,2,3,4].
Soluble GSTs activate glutathione (GSH) to GS-. In many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulfur of GSH. These enzymes catalyze nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom [3].
Soluble glutathione S-transferases are mostly homodimers, with each monomer folding into two distinct domains, an N-terminal thioredoxin-like domain and a C-terminal domain (see <PDB:1GSS>) [5]. The N-terminal domain participate in binding the glutathione moiety via its thioredoxin-like domain while the C-terminal domain contains several hydrophobic α-helices that specifically bind hydrophobic substrates.
To recognize soluble glutathione S-transferase we developed two profiles, one that covers the whole N-terminal domain and one that spans the entire C-terminal domain.
Last update:December 2007 / First entry.
-------------------------------------------------------------------------------
PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Mannervik B. Danielson U.H. |
| Title | Glutathione transferases--structure and catalytic activity. | |
| Source | CRC Crit. Rev. Biochem. 23:283-337(1988). | |
| PubMed ID | 3069329 |
| 2 | Authors | Coles B. Ketterer B. |
| Title | The role of glutathione and glutathione transferases in chemical carcinogenesis. | |
| Source | Crit. Rev. Biochem. Mol. Biol. 25:47-70(1990). | |
| PubMed ID | 2182291 |
| 3 | Authors | Mannervik B. Board P.G. Hayes J.D. Listowsky I. Pearson W.R. |
| Title | Nomenclature for mammalian soluble glutathione transferases. | |
| Source | Methods Enzymol. 401:1-8(2005). | |
| PubMed ID | 16399376 | |
| DOI | 10.1016/S0076-6879(05)01001-3 |
| 4 | Authors | Pettersson P.L. Thoren S. Jakobsson P.J. |
| Title | Human microsomal prostaglandin E synthase 1: a member of the MAPEG protein superfamily. | |
| Source | Methods Enzymol. 401:147-161(2005). | |
| PubMed ID | 16399384 | |
| DOI | 10.1016/S0076-6879(05)01009-8 |
| 5 | Authors | Le Trong I. Stenkamp R.E. Ibarra C. Atkins W.M. Adman E.T. |
| Title | 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site. | |
| Source | Proteins 48:618-627(2002). | |
| PubMed ID | 12211029 | |
| DOI | 10.1002/prot.10162 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)