Oxidation of cysteine

Tertiary structure also refers to the overall shape of a molecule, especially to structures stabilized by disulfide bridges (cystine) formed by the oxidation of cysteine mercapto groups. 

Cysteic acid (3-sulfoalanine, l-amino-3-sulfopropionic acid) [13100-82-8, 3024-83-7] M 169.2, m 260"(dec). Likely impurities are cystine and oxides of cysteine. Crystd from water by adding 2 volumes of EtOH. When recrystd from aqueous MeOH it has m 264-266°, and the anhydrous acid has m 260°(dec). [Chapeville and Formageot Biochim Biophys Acta 26 538 1957 J Biol Chem 72 435 1927.]... 

Garner, M.H. and Spector, A. (1980). Selective oxidation of cysteine and methionine residues in normal and senile cataractous lenses. Proc. Natl Acad. Sci. USA 77, 1274-1277. 

Schweers O, Mandelkow EM, Biemat J, Mandelkow E. Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proc Natl Acad Sci USA 1995 92 8463-8467. 

Fig. 3. Decay of the H202 concentration versus time during the anaerobic oxidation reaction with cysteine in the presence of CuS04. First stage of constant rate (first-order in [Cu]) during the period of oxidation, second stage of increasing rate after completion of the oxidation of cysteine to cystine. Reprinted from Journal of Molecular catalysis, vol. 11, Zwart, J. van Wolput, J. H. M. C. van der Cammen, J. C. J. M. Koningsberger, D. C. Accumulation and Reactions of H202 During the Copper Ion Catalyzed Autoxidation of Cysteine in Alkaline Medium, p. 69, Copyright (2002), with permission from Elsevier Science.

The oxidation of cysteine, as well as other amino acids, was studied by Mudd et a/. Individual amino acids in aqueous solution were exposed to ozone the reported order of susceptibility was cysteine, methionine, tryptophan, tyrosine, histidine, cystine, and phenylalanine. Other amino acids were not affected. This order is similar to that for the relative susceptibility of amino acrids to radiation and to lipid peroxides. Evaluation of the ozonization products revealed that cysteine was converted to cysteic acid, as well as cystine methionine to methionine sulfoxide tryptophan to a variety of pioducrts, including kynurenine and N-formylkynurenine tyrosine also to a variety of products, includiitg dihydroxyphenylalanine histidine to ammonia, proline, and other compounds and cystine in part to cysteic acid. In some cases, the rate and end products depended on the pH of the solution. 

A further development of the DMSO/H+ method for oxidation of cysteine peptides led to the cysteine-sulfoxide acid-catalyzed intermolecular disulfide formation with a second S-unprotected or acid-labile protected cysteine component as shown in Scheme 19. 1471 The protonation of the sulfoxide by TfOH in the case of 5(0)-Mob or TFA in the case of 5(0)-Acm derivatives provides electrophilicity to the sulfur atom to allow attack by the second S-unprotected cysteine component (formed by the fast deprotection of the 5-Mob group with TfOH in presence of dimethylsulfide) to generate in a site-directed manner the interchain disulfide bond. Although extensive experience with this method has not been accumulated for interchain disulfide bridging, it has been successfully applied for intrachain site-directed disulfide bond formation in chicken calcitonin-gene-related peptide.1 79 ... 

It should be stated here that the suggestion of Cu(III) as the oxidation state in different oxidation and autoxidation reactions does not exclude the participation of Cu(II)-Cu(I) couple in other reactions, where Cu(II) is easily reduced by the substrate-e.g., iodide or sulfite ions (4). Likewise, the Co(II)-Co(III) couple was shown to operate in the oxidation of cystein (69), which was shown to proceed according to... 

The spontaneous reaction of nitric oxide with thiols is slow at physiological pH and the final product under anaerobic conditions is not a nitrosothiol (Pryor et al., 1982). The reaction is slow because it involves the conjugate base of the thiol (R—S"). At pH 7.0, the oxidation of cysteine by nitric oxide required 6 hr to reach completion and yields RSSR and N 2O as the products. The synthetic preparation of nitrosothiols usually involves the addition of nitrosonium ion from acidified nitrite to the thiol, or oxidation of the thiol with nitrogen dioxide under anaerobic conditions in organic solvents. Nitric oxide will form nitrosothiols by reaction with ferric heme groups, such as found in metmyoglobin or methemoglobin (Wade and Castro, 1990). It is also possible that nitrosyldioxyl radical also reacts with thiols to form a nitrosothiol. 

NO reacts very efficiently with superoxide to form peroxynitrite (ONOO-), a highly reactive oxidant that leads to DNA damage, nitration of tyrosine, and oxidation of cysteine to disulfides or to various sulfur oxides (SOx). Several cellular... 

Experimental observations indicate that the oxidation of cobalt (II) to cobalt (III) and the formation of ethylenediamine from N-hydroxyethylethylene-diamine occur simultaneously. This is quite the opposite to what is usually assumed in other instances of transition metal catalysis of organic reactions—for example, the catalytic effect of manganese in the oxidation of oxalic acid (7, 8), of iron in the oxidation of cysteine to cystine (22) and of thioglycolic acid to dithioglycolic acid (5, 23), of copper in the oxidation of pyrocatechol to quinone and in the oxidation of ascorbic acid (29, 30), and of cobalt in the oxidation of aldehydes and unsaturated hydrocarbons (4). In all these reactions the oxidation of the organic molecule occurs by the abstraction of an electron by the oxidized form of the metal ion. 

An interesting study (85) explores the use of sodium azide as an oxidative agent instead of performic acid. The big advantage offered here is that the oxidation of cysteine to cysteic acid is effected concurrent with the hydrochloric acid hydrolysis. The authors claim that the presence of 0.2% (w/v) NaN3 in the HC1 digestion does not represent an explosion risk. Recoveries of cysteine as cysteic acid were typically —90% for pure proteins. 

A reversible covalent modification that plants use extensively is the reduction of cystine disulfide bridges to sulf-hydryls. Many of the enzymes of photosynthetic carbohydrate synthesis are activated in this way (table 9.3). Some of the enzymes of carbohydrate breakdown are inactivated by the same mechanism. The reductant is a small protein called thioredoxin, which undergoes a complementary oxidation of cysteine residues to cystine (fig. 9.5). Thioredoxin itself is reduced by electron-transfer reactions driven by sunlight, which serves as a signal to switch carbohydrate metabolism from carbohydrate breakdown to synthesis. In one of the regulated enzymes, phosphoribulokinase, one of the freed cysteines probably forms part of the catalytic active site. In nicotinamide-adenine dinucleotide phosphate (NADP)-malate dehydrogenase and fructose-1,6-bis-... 

Scheme 5 Air Oxidation of Cysteine Side Chains To Form a Disulfide Bond and Reaction of Cysteine with NEMl92h b...

The oxidation of glutamic acid to cyanopropionic acid with CAB in acid solution showed an inverse fractional dependence on acidity. Similarly in alkaline medium, the order in alkali is fractional inverse.143 Kinetics of ruthenium(III)-catalysed oxidation of diols with CAB have been obtained. The products arise due to a fission of the glycol bond.144 The oxidation of isatins with CAB, in alkaline solutions, showed a first-order dependence on CAB and isatin and fractional order in alkali. The rates correlate with the Hammett relationship, the reaction constant p being —0.31. The observed results have been explained by a plausible mechanism and the related rate law has been deduced.145 The oxidation of cysteine with CAB in sulfuric acid medium is first order in CAB and cysteine and the rate is decreased with an increase in the hydrogen ion concentration.146... 

Biological oxidation of cysteine gives the disulfide cystine. 

Biological oxidation of cysteine can yield, in addition to the disulfide cystine, cysteine sulfinic acid and the sulfonic acid cysteic acid. 

The oxidation of L-cysteine on MPc (M = Fe, Mn, and Co) linked to 4-mercaptopyridine preformed SAMs (MPc-4-MPy-SAM) occurred at 0.2V, Table 3, with FePc-4-MPy-SAM showing better catalytic activity as judged by higher peak current when compared to CoPc-4-MPy-SAM and MnPc-4-MPy-SAM [86], Long term stability (over a 2-week period) of MPc-4-MPy-SAM (M = Fe, Co, Mn) towards the oxidation of L-cysteine decreased as follows FePc > MnPc > CoPc. Thus, the oxidation of cysteine is less stable on CoPc modified electrode and this complex is less catalytic compared to corresponding MnPc and FePc derivatives. 

There is a wider general interest in understanding the oxidation of cysteine thiolates in proteins since they are involved in redox-sensing reactions [99], Therefore, such oxidation reactions of thiols induced by Ru coordination may also play a more general role in the pharmacological activity of Ru-arene complexes by coupling Ru coordinative binding to redox processes both outside and inside cells. 

Oxidation of Cysteines. Treatment of a protein with performic acid cleaved all the disulfide bonds and converted all Cys residues to cysteic acid residues (Fig. 3-26). 

Such chemical changes may lead to compounds that are not hydrolyzable by intestinal enzymes or to modifications of the peptide side chains that render certain amino acids unavailable. Mild heat treatments in the presence of water can significantly improve the protein s nutritional value in some cases. Sulfur-containing amino acids may become more available and certain antinutritional factors such as the trypsin inhibitors of soybeans may be deactivated. Excessive heat in the absence of water can be detrimental to protein quality for example, in fish proteins, tryptophan, arginine, methionine, and lysine may be damaged. A number of chemical reactions may take place during heat treatment including decomposition, dehydration of serine and threonine, loss of sulfur from cysteine, oxidation of cysteine and methio-... 

Moriarty-Craige, S. Adkison, J. Lyim, M. Gensler, G. Bressler, S. Jones, D. Stemberger, P. 2005. Antioxidant supplements prevent oxidation of cysteine/ cystine redox inpatients with age-related macular degeneration. Am. J. Ophthalmol. 140 1020-1026. 

The dehydrogenase form of the enzyme is converted to the oxidase form by reversible oxidation of cysteine to form a disulfide bridge. The redox potential of the dehydrogenase form of the enzyme is considerably lower than that of the oxidase form, because the protein confers greater stability on the neutral flavin semiquinone radical (Rajagopalan and Johnson, 1992 Kiskeretal., 1997 Nishino and Okamoto, 2000). 

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