Cysteine sulfenic

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... 

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. 

The two cysteines that are bound trans to the peptide ligands have been found (by X-ray crystallography) to be modified by oxygenation to cysteine-sulfenic acid (Cys-SOH (34)) and cysteine-sulfinic acid (Cys-S02H (35)) derivatives. ... 

Npx and Nox use a stable cysteine-sulfenate redox center, in concert with FAD, in catalysis (16). In Npx, the sulfenate form of the resting enzyme is reduced by NADH via the flavin, producing a thiolate ... 

In addition, on exposure of reduced hydrogenases to O2, reactive oxygen species such as superoxide and peroxide are produced, and these can cause other destructive reactions. Crystallography has shown that some cysteine residues in the active site can also become oxidized to cysteine sulfenic acid (29). 

By utilizing a molecular cavity, the chemical transformations associated with a sulfenic acid were extensively investigated. Sulfenic acids are generally assumed to be transient intermediates in the oxidation of thiols, both to disulfides and to sul-finic acids (Scheme 11.10). From a biological view, the redox processes between cysteine thiols and cysteine sulfenic acids play key roles in the redox regulation systems. ... 

In a weakly alkaline solution, isothiocyanate reacts with the a-amino group of cysteine (Figure 2.64). The reaction of isothiocyanates with cystine leads to the cleavage of disulfide bond (-S-S-) with the formation of cysteine sulfenic acid and a dithiocarbamic acid ester. Dehydration of this ester yields 5-amino-l,3-thiazine-4-one-3-thione derivative and elimination of hydrogen sulfide produces a cyclic 2-thiazoline-4-carboxylic acid derivative (Figure 2.65). Reaction of cystine with thiocyanates (R-S-C=N), formed by spontaneous isomerisation of isothiocyanates, produces disulfide Cys-S-S-R and -thiocyanoalanine, which cyclises to 2-thiazoline derivative (Figure 2.66). 

A primary experimental fact relating to this reaction is the formation of sulfate (under aerobic conditions) from cysteine sulfinic acid by the action of ground or extracted rat livers (85). This oxidation was carried out by Medes (85) in order to study the existence of a sulfinic acid oxidase responsible for the action. But it is difficult to assume that a single enzyme would have the ability to split the cysteinesulfinic acid into an organic molecule without sulfur and into inorganic sulfur, and then oxidize the latter to sulfate. Numerous explanations have been proposed to resolve this difficulty. According to Pirie (95), the removal of the sulfur from cysteine-sulfenic acid would take place as sulfite, which in turn would be oxidized spontaneously to sulfate (reaction 31). Medes and Floyd (86) have two other theories to explain the sulfate formation. The first of these two theories may be written ... 

Proton Pump Inhibitors and Acid Pump Antagonists. Figure 2 Chemical mechanism of irreversible PPIs. PPIs are accumulated in acidic lumen and converted to active sulfenic acid and/or sulfenamide by acid catalysis. These active forms bind to extracytoplasmic cysteines of the gastric H.K-ATPase [3]. 

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... 

This enzyme [EC 4.4.1.4], also known as alliinase and cysteine sulfoxide lyase, catalyzes the conversion of an 5-alkyl-L-cysteine 5-oxide to an alkyl sulfenate and 2-aminoacrylate. The enzyme requires pyridoxal phosphate. 

Additional processing of the hexachlorobutadiene metabolites produces the compounds identified in the urine (1,1,2,3-tetrachlorobutenoicacid, 1,1,2,3,4-pentachloro-1 3-butadienyl sulfenic acid, N-acetyl-S-1,1,2,3,4-pentachlorobutadienyl-L-cysteine,... 

The oxidation of co-ordinated cysteine ligands may also give a variety of products. The most usually encountered reactions involve the formation of sulfenate or sulfinate as above however, in some cases disulfide formation occurs in preference to oxygen transfer. In the example shown in Fig. 9-39, the formation of the disulfide is accompanied by decarboxylation of the amino acid ... 

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]. 

As the H+, K+-ATPase inhibition is associated with the modification of mer-capto groups in the enzyme, the disulfide adduct (ESSR) can be considered as a model of the enzyme-inhibitor complex, and the sulfenamide, or possibly the sulfenic acid (C), formed from omeprazole can be considered to be the active inhibitor, which binds covalently to cysteine residues of the H+, K+-ATPase. 

The second molecule of cysteine and a sulfinic acid result from the disproportionation of two molecules of a sulfenic acid (Equation 11). 

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