Cysteine thiyl

The intramolecular addition of cysteine thiyl radicals (CysS ) to phenylalanine yielding alkylthio-substituted cyclohexadienyl radicals was observed in Cys-Phe and Phe-Gly-Cys-Gly peptides.CysS radicals were generated by pulse irradiation of aqueous solution containing the respective disuHide-linked peptide [reactions (11)-(14)] ... 

Nauser T, Casi G, Koppenol WH, Schoneich C. (2005) Intramolecular addition of cysteine thiyl radicals to phenylalanine in peptides Formation of cyclohexadi-enyl type radicals. Chem Comms 3400-3402. 

Nauser T, Casi G, Koppenol W, Schoneich C. (2008) Reversible intramolecular hydrogen transfer between cysteine thiyl radicals and glycine and alanine in model peptides Absolute rate constants derived from pulse radiolysis and laser flash photolysis. JPhys Chem B 112 15034-15044. 

The reaction begins with the transfer of an electron from a cysteine residue on R1 to the tyrosyl radical on R2. The loss of an electron generates a highly reactive cysteine thiyl radical within the active site of Rl. 

Figure 25.11 Ribonucleotide reductase mechanism. (1) An electron is transferred from a cysteine residue on R1 to a tyrosine radical on R2. generating a highly reactive cysteine thiyl radical. (2) This radical abstracts a hydrogen atom from C-3 of the ribose unil. (3) The radica at C-3 releases OH from the C-2 carbon atom. Combined with a proton from a second cysteine residue, the OH is eliminated as water. (4) A hydride ion is transferred from a third cysteine residue with the concomitant formation of a disulfide bond. (5) The C-3 radical recaptures the originally abstracted hydrogen atom. (6) An electron is transferred from R2 to reduce the thiyl radical, which also accepts a proton. The deoxyribonucleotide is free to leave Rl. The disulfide formed in the active site must be reduced to begin another cycle.

Several enzymes utilize thiyl radicals for substrate conversion. In the ribonucleotide reductase (RNR) class III, pyruvate formate lyase and benzylsuccinate synthase, cysteine thiyl radicals are generated via hydrogen transfer from cysteine to glycine radicals (Reaction (3.25)) [3, 24-27, 48-52]. 

Figure 6. Mechanism of cysteine-fatty acid adduct formation from the reaction of 13-hydroperoxylinoleic acid and cysteine in the absence of O2. The epoxyallylic radical at the top originates from the oxydiene radical of 13-hydroperoxylinoleic acid abbreviated structure) and RS is the cysteine thiyl radical. Reproduced with permission from Ref. 28.)...

Reaction P is very similar to the combination reaction of lipid oxy radical with the cysteine thiyl radical (Fig. 6). Both combination reactions proceed only in the absence of O2, implying the Og effectively competes for the radicals involved. 

Figure 2. Potential energy surface for the cysteine thiyl radical resulting from a constrained geometry optimization with respect to the C-Ca-Cp-Sy dihedral angle. Reproduced with permission from [128]. Copyright 2004, American Chemical Society.

Figure 3. Overview of the three geometry-optimized structures of the cysteine thiyl radical, (a) 1st minimum, (b) 2nd minimum, and (c) 3rd minimum. The directions of the principal axes of the g-tensor z (brown, parallel to the synunetry axis of the 3p orbital in the SOMO) and the y (light-blue) principal axis of the g-tensor are indicated. The x axis is parallel to the Cp-Sy direction. Reproduced with pemussion from [128]. Copyright 2004, American Chemical Society.

The degradation of tetrachloromethane by a strain of Pseudomonas sp. presents a number of exceptional features. Although was a major product from the metabolism of CCI4, a substantial part of the label was retained in nonvolatile water-soluble residues (Lewis and Crawford 1995). The nature of these was revealed by the isolation of adducts with cysteine and A,A -dimethylethylenediamine, when the intermediates that are formally equivalent to COClj and CSClj were trapped—presumably formed by reaction of the substrate with water and a thiol, respectively. Further examination of this strain classified as Pseudomonas stutzeri strain KC has illuminated novel details of the mechanism. The metabolite pyridine-2,6-dithiocarboxylic acid (Lee et al. 1999) plays a key role in the degradation. Its copper complex produces trichloromethyl and thiyl radicals, and thence the formation of CO2, CS2, and COS (Figure 7.64) (Lewis et al. 2001). 

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... 

Conversion of ribonucleotides to deoxyribonucleotides is an important process that occurs by several pathways, and in one of these, tyrosyl radicals 71 are formed, which serve to generate thiyl radicals from cysteine residues (equation A mechanism for this process has been proposed by... 

Sevilla MD, Becker D, Yan M (1990a) The formation and structure of the sulfoxyl radicals RSO, RSOO, RSCV, and RS0200 from the reaction of cysteine, glutathione and penicillamine thiyl radicals with molecular oxygen. Int J Radiat Biol 57 65-81... 

The most comprehensive set of kinetic studies on AdoCbl homolysis have been performed with AdoCbl-dependent ribonucleotide reductase by Stubbe and coworkers (Licht et al., 1999a Licht et al., 1999b). In this enzyme, AdoCbl is used to generate a thiyl radical on a cysteine residue it is this thiyl radical that abstracts hydrogen from the 3-position of the ribonucleotide to faeilitate reduction at C-2. In the presence of dGTP, an allosteric activator of the enzyme, the enzyme catalyzes the reversible cleavage of AdoCbl and formation of thiyl radical in the absence of substrate. This partial reaction proceeds rapidly enough for it to be mechanistically relevant and provides a system to study AdoCbl homolysis which is both simple and amenable to detailed kinetic analysis. 

The second mechanism is due to Kozarich and co-workers [39] (Figure 11). The initial step here is the abstraction of a hydrogen atom from Cys419 by the glycyl radical, forming a transient thiyl radical. Addition of this thiyl radical to the keto group of the pyruvate results in the formation of a tetrahedral oxy-radical intermediate. This intermediate collapses into an acetylated cysteine and... 

The next step is the addition of the thiyl radical to the carbonyl carbon of pyruvate, yielding a tetrahedral oxy-radical intermediate. The calculated energy of this intermediate, relative to the free reactants, is +9.9 kcal/mol, and the barrier for its formation is calculated to 12.3 kcal/mol. The barrier for the dissociation of the radical intermediate into acetylated cysteine and formyl radical is calculated to be only 2.8 kcal/mol with an exothermicity of 3.9 kcal/mol. Taken together, the total reaction ... 

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