Molecular Mechanisms of Glutaredoxin Enzymes: Versatile Hubs for Thiol–Disulfide Exchange between Protein Thiols and Glutathione. Issue 2 (18th January 2019)

• Record Type: Journal Article
• Authors: Xiao, Zhiguang; La Fontaine, Sharon; Bush, Ashley I.; Wedd, Anthony G.
• Is Part Of: Journal of molecular biology. Volume 431:Issue 2(2019)
• Page Start: 158
• Page End: 177
• Publication Date: 2019-01-18
• Subjects: DsbA disulfide bond protein A -- Grxs glutaredoxins -- GSH glutathione -- GSSG glutathione disulfide -- HEDS bis(2-hydroxyethyl)disulfide -- SOD superoxide dismutase -- NADP+ nicotinamide adenine dinucleotide phosphate -- NADPH the reduced form of NADP+ -- PDI protein disulfide-isomerase -- RNR ribonucleotide reductase -- ROS reactive oxygen species -- Trxs thioredoxins -- TrxR thioredoxin reductase; glutaredoxin -- glutathione -- molecular mechanism -- redox homeostasis -- thiol–disulfide exchange -- metal binding; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.12.006
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The tripeptide glutathione (GSH) and its oxidized form glutathione disulfide (GSSG) constitute a key redox couple in cells. In particular, they partner protein thiols in reversible thiol–disulfide exchange reactions that act as switches in cell signaling and redox homeostasis. Disruption of these processes may impair cellular redox signal transduction and induce redox misbalances that are linked directly to aging processes and to a range of pathological conditions including cancer, cardiovascular diseases and neurological disorders. Glutaredoxins are a class of GSH-dependent oxidoreductase enzymes that specifically catalyze reversible thiol–disulfide exchange reactions between protein thiols and the abundant thiol pool GSSG/GSH. They protect protein thiols from irreversible oxidation, regulate their activities under a variety of cellular conditions and are key players in cell signaling and redox homeostasis. On the other hand, they may also function as metal-binding proteins with a possible role in the cellular homeostasis and metabolism of essential metals copper and iron. However, the molecular basis and underlying mechanisms of glutaredoxin action remain elusive in many situations. This review focuses specifically on these aspects in the context of recent developments that illuminate some of these uncertainties. Graphical Abstract: Unlabelled Image Highlights: Glutaredoxins are a class of glutathione-dependent thiol–disulfide oxidoreductase enzymes. Glutaredoxins facilitate reversible redox chemistry between glutathione and protein thiols. Glutaredoxins employ parallel and flexible monothiol–dithiols mechanism in catalysis. Glutaredoxins are versatile players in cellular redox signaling and redox homeostasis. Glutaredoxins may assist copper and iron homeostasis and metabolism.