ArticleThe Journal of biological chemistry2012
A low pKa cysteine at the active site of mouse methionine sulfoxide reductase A.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
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- Proteome-wide detection of S-nitrosylation targets and motifs using bioorthogonal cleavable-linker-based enrichment and switch technique.Nature communications · 2019Article
- Redox Signaling by Reactive Electrophiles and Oxidants.Chemical reviews · 2018Review
- A structural and mechanistic study of π-clamp-mediated cysteine perfluoroarylation.Scientific reports · 2017Article
- Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31.The Journal of pharmacology and experimental therapeutics · 2017Article
- A Methionine Residue Promotes Hyperoxidation of the Catalytic Cysteine of Mouse Methionine Sulfoxide Reductase A.Biochemistry · 2016Article
- Site-Specific Proteomic Mapping Identifies Selectively Modified Regulatory Cysteine Residues in Functionally Distinct Protein Networks.Chemistry & biology · 2015Article
- Mechanism of oxidative inactivation of human presequence protease by hydrogen peroxide.Free radical biology & medicine · 2014Article
- pH-dependent random coil (1)H, (13)C, and (15)N chemical shifts of the ionizable amino acids: a guide for protein pK a measurements.Journal of biomolecular NMR · 2014Article
- Thiol redox biochemistry: insights from computer simulations.Biophysical reviews · 2014Review
- Detection of electrophile-sensitive proteins.Biochimica et biophysica acta · 2014Review
- Strategies for profiling native S-nitrosylation.Biopolymers · 2014Review
- Methionine oxidation and reduction in proteins.Biochimica et biophysica acta · 2014Review
- Stereospecific oxidation of calmodulin by methionine sulfoxide reductase A.Free radical biology & medicine · 2013Article
- Protein Oxidative Modifications: Beneficial Roles in Disease and Health.Journal of biochemical and pharmacological research · 2013Article
- The role of methionine sulfoxide reductase in redox signaling.The Journal of biological chemistry · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Methionine sulfoxide reductase A is an essential enzyme in the antioxidant system which scavenges reactive oxygen species through cyclic oxidation and reduction of methionine and methionine sulfoxide. Recently it has also been shown to catalyze the reverse reaction, oxidizing methionine residues to methionine sulfoxide. A cysteine at the active site of the enzyme is essential for both reductase and oxidase activities. This cysteine has been reported to have a pK(a) of 9.5 in the absence of substrate, decreasing to 5.7 upon binding of substrate. Using three independent methods, we show that the pK(a) of the active site cysteine of mouse methionine sulfoxide reductase is 7.2 even in the absence of substrate. The primary mechanism by which the pK(a) is lowered is hydrogen bonding of the active site Cys-72 to protonated Glu-115. The low pK(a) renders the active site cysteine susceptible to oxidation to sulfenic acid by micromolar concentrations of hydrogen peroxide. This characteristic supports a role for methionine sulfoxide reductase in redox signaling.
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