Reactions of Thiols with Sulfoxides. II. Kinetics and Mechanistic Implications

Wallace, Thomas J.; Mahon, John J.

doi:10.1021/ja01073a039

Cited by 84 publications

(52 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reactions of small molecule sulfoxides with thiols have been extensively studied (26)(27)(28)(29). The slow step (step 1) is considered to be the attack on the sulfur atom of the sulfoxide by the thiol.…”

Section: Discussionmentioning

confidence: 99%

Thiol–disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase

Lowther

Brot

Weissbach

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

162

183

View full text Add to dashboard Cite

Peptide methionine sulfoxide reductase (MsrA; EC 1.8.4.6) reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulfoxide, Met(O), to methionine. MsrA activity is independent of bound metal and cofactors but does require reducing equivalents from either DTT or a thioredoxin-regenerating system. In an effort to understand these observations, the four cysteine residues of bovine MsrA were mutated to serine in a series of permutations. An analysis of the enzymatic activity of the variants and their free sulfhydryl states by mass spectrometry revealed that thioldisulfide exchange occurs during catalysis. In particular, the strictly conserved Cys-72 was found to be essential for activity and could form disulfide bonds, only upon incubation with substrate, with either Cys-218 or Cys-227, located at the C terminus. The significantly decreased activity of the Cys-218 and Cys-227 variants in the presence of thioredoxin suggested that these residues shuttle reducing equivalents from thioredoxin to the active site. A reaction mechanism based on the known reactivities of thiols with sulfoxides and the available data for MsrA was formulated. In this scheme, Cys-72 acts as a nucleophile and attacks the sulfur atom of the sulfoxide moiety, leading to the formation of a covalent, tetracoordinate intermediate. Collapse of the intermediate is facilitated by proton transfer and the concomitant attack of Cys-218 on Cys-72, leading to the formation of a disulfide bond. The active site is returned to the reduced state for another round of catalysis by a series of thiol-disulfide exchange reactions via Cys-227, DTT, or thioredoxin.oxidation ͉ cysteine ͉ thioredoxin ͉ Alzheimer's disease ͉ aging

show abstract

Section: Discussionmentioning

confidence: 99%

Thiol–disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase

Lowther

Brot

Weissbach

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

162

183

View full text Add to dashboard Cite

show abstract

“…Glu115 acts as a proton donor to the sulfoxide, and the protonated hydroxyl sulfonium intermediate (III) is stabilized by hydrogen bonding with Tyr103. Nucleophilic attack of the hydroxyl sulfonium intermediate by the thiolate of Cys72 forms the sulfurane intermediate (IV) (42)(43)(44). It has been suggested that the sulfurane hydroxyl group could be protonated by a second methanthiol molecule and form the sulfonium intermediate upon loss of water.…”

Section: Methodsmentioning

confidence: 99%

Methionine sulfoxide reductase A is a stereospecific methionine oxidase

Lim

You

Kim

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

Methionine sulfoxide reductase A (MsrA) catalyzes the reduction of methionine sulfoxide to methionine and is specific for the S epimer of methionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing methionine sulfoxide residues in proteins back to methionine. Because oxidation of methionine residues is reversible, this covalent modification could also function as a mechanism for cellular regulation, provided there exists a stereospecific methionine oxidase. We show that MsrA itself is a stereospecific methionine oxidase, producing S-methionine sulfoxide as its product. MsrA catalyzes its own autooxidation as well as oxidation of free methionine and methionine residues in peptides and proteins. When functioning as a reductase, MsrA fully reverses the oxidations which it catalyzes.

show abstract

“…For the oxidation of thiophenol (XId) to phenyl disulfide (XIId), it was not necessary to use the hiloffatt reagent, since treatment with DMSO alone a t roorn temperature (18) gave the disulfide in a quantitative yield.…”

Section: C Analytical Methods Alone For Follozoing Their Reactionsmentioning

confidence: 99%

“…Since treatinent of thiols with DNISO alone, usually for an extended period or a t a n elevated temperature, is Itnown (18) to give the corresponding disulfides in a good yield, 5T1~e use of the zisz~ally reliable t.…”

mentioning

confidence: 99%

Steroids and Steroidases: Iii. Dicyclohexylcarbodiimide–dimethyl Sulfoxide Oxidations of Alcohols and Thiols

Jones¹,

Wigfield²

1966

Can. J. Chem.

View full text Add to dashboard Cite

A survey of methods for the preparation of acid- and base-labile steroid Δ5-3-ketones showed that oxidation of the appropriate Δ5-3β-alcohols with dicyclohexylcarbodiimide–dimethyl sulfoxide (Moffatt reagent) was the most satisfactory, giving yields of 60–70% of the required ketones with little or no isomerization to the corresponding Δ4-3-ketones. From the oxidation of 3β-hydroxyandrost-5-en-17-one, the product of a Pummerer rearrangement, 3β-(methylthiomethoxy)-androst-5-en-17-one, was isolated. The Moffatt reagent also was convenient for the oxidation of thiols to the corresponding disulfides.

show abstract

Reactions of Thiols with Sulfoxides. II. Kinetics and Mechanistic Implications

Cited by 84 publications

References 1 publication

Thiol–disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase

Thiol–disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase

Methionine sulfoxide reductase A is a stereospecific methionine oxidase

Steroids and Steroidases: Iii. Dicyclohexylcarbodiimide–dimethyl Sulfoxide Oxidations of Alcohols and Thiols

Contact Info

Product

Resources

About