Thiol:disulfide oxidoreductases

Aslund, E, Bemdt, K.D., Holmgren, A. Redox potentials of glutaredoxins and other thiol-disulfide oxidoreductases of the thioredoxin superfamily determined by direct protein-protein redox equilibria. J Biol Chem 272(49), 30780-30786 (1997)... 

Both thioredoxin and glutaredoxin are members of a larger group of thiol disulfide oxidoreductases which are found in all known organisms. In E. coli there are one thioredoxin, three different glutaredoxins,h/t and the periplasmic protein disulfide... 

Thioredoxin behaves differently from other proteins. Because of the great interest of the sulphur function in this enzyme (it is the active site of this thiol-disulfide oxidoreductase), the reduction of oxidized thioredoxin was studied in detail (139, 140). The disulfide radical is much more acidic than in other proteins, and its decay leads only to the reduced protein. Site-directed mutagenesis was used to modify selectively two amino-acids, Asp30 and Trp35, in order to observe the modulation of the redox properties of the sulphur functions. It was thus shown that both residues play a role in the proton transfer associated to electron transfer, although differently for instance, removal of W35 increases the pKa of... 

The N-terminal signal peptides of precursor proteins are cleaved by SPases during or shortly after translocation via the Sec apparatus. Only after translocation through the Sec apparatus has been completed are the secreted proteins folded into a biologically active conformation by chaperones, such as the lipoprotein PrsA [57] or the thiol-disulfide oxidoreductases BdbB, BdbC, and BdbD [58,... 

Thioredoxin, a thiol-disulfide oxidoreductase, is possibly involved in antioxidant protection in human coronary arteries (424). Exercise-induced plasma oxidative stress could be responsible for the prevention of atherosclerosis by stimulating arterial antioxidant response. In addition, vitamin E could be deleterious in exercisers by inhibiting antioxidant enzyme buildup in the arterial wall in LDL receptor -/- male mice fed an atherogenic diet (425). 

Zhou, L., McKenzie, B. A., Eccleston, E. D., Jr, Srivastava, S. R, Chen, N., Erickson, R. R., Holtzman, J. L. The covalent binding of [ C]acetaminophen to mouse hepatic microsomal proteins the specific binding to calreticulin and the two forms of the thiol rprotein disulfide oxidoreductases. Chem. Res. Toxicol. 1996, 9,1176—1182. 

Proteins from hyperthermophilic archaea usually contain a decreased number of cysteine residues compared to their mesophilic counterparts. This is probably due to the easy oxidation and instability of sulfur-containing amino acid residues at high temperatures. Consequently, there have been arguments, although with little supportive evidence, that archaeal proteins contain hardly any disulfide bonds. However, a few protein disulfide oxidoreductases have been purified and characterized in archaea. Their existence suggests that thiol-disulfide exchange reactions actually take place in archaea as in bacteria and eukarya. The determination of the first three-dimensional structure of a protein disulfide oxidoreductase from the archaeon Pyrococcus furiosus (P/PDO) has provided the first view of active site disulfides in an archaeal protein. It reveals a unique structural form compared to those of protein disulfide oxidoreductases in bacteria and eukarya. 

In neural cells, the redox status is controlled by the thioredoxin (Trx) and glutathione (GSH) systems that scavenge harmful intracellular ROS. Thioredoxins are antioxidants that serve as a general protein disulphide oxidoreductase (Saitoh et al., 1998). They interact with a broad range of proteins by a redox mechanism based on the reversible oxidation of 2 cysteine thiol groups to a disulphide, accompanied by the transfer of 2 electrons and 2 protons. These proteins maintain their reduced state through the thioredoxin system, which consists of NADPH, thioredoxin reductase (TR), and thioredoxin (Trx) (Williams, Jr. et al., 2000 Saitoh et al., 1998). The thioredoxin system is a system inducible by oxidative stress that reduces the disulfide bond in proteins (Fig. 7.4). It is a major cellular redox system that maintains cysteine residues in the reduced state in numerous proteins. 

FAD-dependent disulflde oxidoreductases contain active-site thiols. They use a dithiol substrate and NAD+ to form a disulfide product and NADH or act in the reverse direction yielding... 

The thiol group of Cys is the most reactive side residue. The thiolate anion is a potent nucleophile and the thiol is a week acid with pKj = 8.37. Cys serves as the active site residues of many oxidoreductases. Cys residues form complexes of varying stability with a variety of metal ions. It reacts with organic mercurials stoichiometiically. Thiol residues of Cys cross link to form disulfide bonds (cystine) in proteins. Thiols and disulfides undergo rapid exchange and redox reactions. 

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