Protein sulfenic acids

Claiborne A, Yeh JI, Mallett TC, Luba J, Crane EJ HI, Charrier V, Parsonage D (1999) Protein-sulfenic acids diverse roles for an unlikely player in enzyme catalysis and redox regulation. Biochemistry 38 15407-15416... 

Poole LB, Karplus PA, Claiborne A (2004) Protein sulfenic acids in redox signaling. Annu Rev Pharmacol Toxicol 44 325-347... 

Claiborne A, Miller H, Parsonage D, Ross RP (1993) Protein-sulfenic acid stabilization and function in enzyme catalysis and gene regulation. Faseb J 7 1483-1490... 

Protein thiols can interact with glutathione by several mechanisms that permit glu-tathionylation to participate in the regulation and antioxidant protection of specific protein thiols. These reactions are involved in the consequences of oxidative stress caused by reactive species of oxygen and nitrogen and include the formation of protein sulfenic acids and their participation in regulatory processes. 

Peroxiredoxins Group of antioxidant thioredoxin-dependent enzymes with a catalytic fnnc-tion in the detoxification of cellnlar-toxic peroxides. See Claiborne, A., Ross, R.P., and Parsonage, D., Flavin-linked peroxide rednctases protein-sulfenic acids and the oxidative stress response. Trends Biochem. Sci. 17, 183-186, 1992 Dietz, K-J., Horhing, R, Konig, J., and Baien, M., The function of chloroplast 2-cysteine peroxiredoxin I peroxide detoxification and its regulation, J. Expt. Bot. 53, 1321-1329, 2002 Immenschuh, S. 

Poole LB, Karplus PA, Claiborne A. Protein sulfenic acids in redox signaling. Annu. Rev. Pharmacol. Toxicol. 2004 44 325-347. Pollegioni L, Piubelli L, Sacchi S, Pilone MS, Molla G. Physiological functions of D-amino acid oxidases from yeast to humans. Cell. Mol. Life Sci. 2007 64 1373-1394. 

Roos G, Messens J (2011) Protein sulfenic acid formation from cellular damage to redox regulation. Free Radic Biol Med 51 314-326... 

Peroxynitrite easily oxidizes nonprotein and protein thiyl groups. In 1991, Radi et al. [102] have shown that peroxynitrite efficiently oxidizes cysteine to its disulfide form and bovine serum albumin (BSA) to some derivative of sulfenic acid supposedly via the decomposition to nitric dioxide and hydroxyl radicals. Pryor et al. [124] suggested that the oxidation of methionine and its analog 2-keto-4-thiomethylbutanic acid occurred by two competing mechanisms, namely, the second-order reaction of sulfide formation and the one-electron... 

Disulfides can be reduced to two thiols (Fig. 5.14). The best example is the reduction of oxidized glutathione (GSSG) back to the reduced form (GSH) (Fig. 5.14), which is mediated by glutathione reductase. In addition, exchange can occur with other thiols mediated by protein disulfide isomerase. In principle, sulfenic acids can probably also be reduced back to thiols, but because of the reactivity of the sulfenic acid, this is not generally observed. 

When applied to whole HeLa cells, 193 proteins were identified, with diverse biological functions including signal transduction, protein synthesis, and chaperone-mediated protein folding. Of the proteins identified in this study, 56% were not previously reported to possess redox-active cysteines, and 93% were not reported to undergo sulfenic acid modification [172]. 

Claiborne A, Mallett TC, Yeh JI, Luba J, Parsonage D (2001) Structural, redox, and mechanistic parameters for cysteine-sulfenic acid function in catalysis and regulation. Adv Protein Chem 58 215-276... 

Hydrogen peroxide commonly is used to oxidize sulfhydryls in proteins to disulfides or, on more extensive treatment, to sulfonic acids (1). However, under certain conditions reacting hydrogen peroxide with protein sulfhydryls may lead to the formation of sulfenic acids (21). The inactivation of highly purified papain by stoichiometric amounts of hydrogen peroxide appears to be due almost exclusively to the formation of papain sulfenic acid (22). The formation and reactions of sulfenic acids in proteins have been reviewed elsewhere by Allison (21). 

Cystine and cysteine also can be oxidized under the same conditions but the analytical methods to detect these oxidation products in proteins have not been developed yet. The different oxidation products of cystine, which have been synthesized (55-58), are cystine disulfoxide (NH2-CH-(COOH)-CH2-SO-SO-CH2-(COOH)-CH-NH2), cystine disul-fone (NH2-CH- (COOH) -CH2-C02-S02-CH2-( COOH )-CH-NH2), cysteine sulfenic acid (NH2-CH-(COOH)-CH2-SOH), cysteine sul-finic acid (NH2-CH-(C00H)-CH2-S02H), and cysteine sulfonic acid or cysteic acid (NH2-CH-(C00H)-CH2-S03H). It is doubtful that all of these derivatives described in 1935 by Bennett are present in proteins. 

Denu JM, Tanner KG. Redox regulation of protein tyrosine phosphatases by hydrogen peroxide detecting sulfenic acid intermediates and examining reversible inactivation. Methods Enzymol. 2002 348 297-305. 

It is well known that the redox responsiveness in proteins may be conferred by S-NO (nitrosylation), S-OH (sulfenic acid), S-S (intramolecular disulfide), and S-SR (mixed disulfide or S-thiolation), all potential reversible modifications of reactive cysteines (Figure... 

Figure 3. The treatment with GSSG produces an inhibition in the DNA binding activity of p50 by S-glutathionylation. A) The DNA binding of pSO was subjected to EMSA experiments in the presence of different GSH/GSSG ratios or DTT. B) In the figure represented the amount of protein which is modified to mixed disulfide with glutathione (P-S-S-G), sulfenic acid (P-SOH) or intermolecular disulfide (P-S-S-P).

J.M. Denu, and K.G. Tanner, Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide evidence for a sulfenic acid intermediate and implications for redox regulation. 

Sulfenic acids (45) are generally quite unstable they easily dimerise and eliminate water to form thiol sulfinates (46) (Scheme 28). Several sulfenic acids have, however, been isolated and many of these are stabilised by hydrogen bonding to a carbonyl or amino group. The first sulfenic acid to be isolated was the anthraquinone derivative (47) in 1912. Sulfenic acids have been postulated as transient intermediates in many chemical and biochemical processes, e.g. the oxidation of thiol groups in proteins and the thermolysis of sulfoxides, including the acid-catalysed rearrangement of penicillin sulfoxides (48) to cephalosporins (49) (Scheme 29)... 

When garlic is mechanically disrupted, alliinase or alliin lyase (EC 4.4.1.4.) catalyzes the conversion of the cysteine sulfoxides to the biologically active diallyl thiosulfinates via sulfenic acid intermediates (Block, 1992). Alliinase is localized to a few vascular bundle sheath cells around the veins or phloem, whereas alliin and other cysteine sulfoxides are found in the clove mesophyll storage cells. This enzyme is approximately 10 times more abundant in the cloves than in the leaves and accounts for at least 10% of the total protein in the cloves (Ellmore and Feldberg, 1994). Alliinase is temperature and pH dependent optimal activity is between pH 5.0-10.0, but allinase can be irreversibly deactivated at pH 1.5-3.0 (Krest and Keusgen, 1999). 

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