| Structural highlights
4is0 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 1eem, 3vln, 3q19, 1gta, 2gsq |
| Gene: | GSTO1, GSTTLP28 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GSTO1_HUMAN] Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel "ligandin" binding site deep within in the dimer interface of this enzyme, containing S-(4-nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors.
Structural insights into omega-class glutathione transferases: a snapshot of enzyme reduction and identification of a non-catalytic ligandin site.,Brock J, Board PG, Oakley AJ PLoS One. 2013 Apr 9;8(4):e60324. doi: 10.1371/journal.pone.0060324. Print 2013. PMID:23593192[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J. Identification, characterization, and crystal structure of the Omega class glutathione transferases. J Biol Chem. 2000 Aug 11;275(32):24798-806. PMID:10783391 doi:10.1074/jbc.M001706200
- ↑ Zakharyan RA, Sampayo-Reyes A, Healy SM, Tsaprailis G, Board PG, Liebler DC, Aposhian HV. Human monomethylarsonic acid (MMA(V)) reductase is a member of the glutathione-S-transferase superfamily. Chem Res Toxicol. 2001 Aug;14(8):1051-7. PMID:11511179
- ↑ Board PG, Anders MW. Glutathione transferase omega 1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones. Chem Res Toxicol. 2007 Jan;20(1):149-54. PMID:17226937 doi:10.1021/tx600305y
- ↑ Board PG, Coggan M, Cappello J, Zhou H, Oakley AJ, Anders MW. S-(4-Nitrophenacyl)glutathione is a specific substrate for glutathione transferase omega 1-1. Anal Biochem. 2008 Mar 1;374(1):25-30. Epub 2007 Sep 29. PMID:18028863 doi:10.1016/j.ab.2007.09.029
- ↑ Zhou H, Brock J, Casarotto MG, Oakley AJ, Board PG. Novel folding and stability defects cause a deficiency of human glutathione transferase omega 1. J Biol Chem. 2011 Feb 11;286(6):4271-9. Epub 2010 Nov 24. PMID:21106529 doi:10.1074/jbc.M110.197822
- ↑ Brock J, Board PG, Oakley AJ. Structural insights into omega-class glutathione transferases: a snapshot of enzyme reduction and identification of a non-catalytic ligandin site. PLoS One. 2013 Apr 9;8(4):e60324. doi: 10.1371/journal.pone.0060324. Print 2013. PMID:23593192 doi:10.1371/journal.pone.0060324
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