title: Structure, function and disease relevance of Omega-class glutathione transferases.
abstract: The Omega-class cytosolic glutathione transferases (GSTs) have distinct structural and functional attributes that allow them to perform novel roles unrelated to the functions of other GSTs. Mammalian GSTO1-1 has been found to play a previously unappreciated role in the glutathionylation cycle that is emerging as significant mechanism regulating protein function. GSTO1-1-catalyzed glutathionylation or deglutathionylation of a key signaling protein may explain the requirement for catalytically active GSTO1-1 in LPS-stimulated pro-inflammatory signaling through the TLR4 receptor. The observation that ML175 a specific GSTO1-1 inhibitor can block LPS-stimulated inflammatory signaling has opened a new avenue for the development of novel anti-inflammatory drugs that could be useful in the treatment of toxic shock and other inflammatory disorders. The role of GSTO2-2 remains unclear. As a dehydroascorbate reductase, it could contribute to the maintenance of cellular redox balance and it is interesting to note that the GSTO2 N142D polymorphism has been associated with multiple diseases including Alzheimer's disease, Parkinson's disease, familial amyotrophic lateral sclerosis, chronic obstructive pulmonary disease, age-related cataract and breast cancer.
authors.affiliation: John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT, 2601, Australia. Philip.board@anu.edu.au.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Board
authors.affiliation: John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT, 2601, Australia.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Menon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; C490476:GSTO1 protein, human; C492569:GSTO2 protein, human; D005982:Glutathione Transferase; D005978:Glutathione
keywords: Dehydroascorbate reductase; GSTO; Glutathione transferase Omega; Glutathionylation; Inflammation