Protein-sulfenic acid stabilization and function in enzyme catalysis and gene regulation.
Sulfenic acids (R-SOH) result from the stoichiometric oxidations of thiols with mild oxidants such as H2O2; in solution, however, these derivatives accumulate only transiently due to rapid self-condensation reactions, further oxidations to the sulfinic and/or sulfonic acids, and reactions with nucleophiles such as R-SH. In contrast, oxidations of cysteinyl side chains in proteins, where disulfide bond formation can be prevented and where the reactivity of the nascent cysteine-sulfenic acid (Cys-SOH) can be controlled, have previously been shown to yield stable active-site Cys-SOH derivatives of papain and glyceraldehyde-3-phosphate dehydrogenase. More recently, however, functional Cys-SOH residues have been identified in the native oxidized forms of the FAD-containing NADH peroxidase and NADH oxidase from Streptococcus faecalis; these two proteins constitute a new class within the flavoprotein disulfide reductase family. In addition, Cys-SOH derivatives have been suggested to play important roles in redox regulation of the DNA-binding activities of transcription factors such as Fos and Jun, OxyR, and bovine papillomavirus type 1 E2 protein. Structural inferences for the stabilization of protein-sulfenic acids, drawn from the refined 2.16-A structure of the streptococcal NADH peroxidase, provide a molecular basis for understanding the proposed redox functions of these novel cofactors in both enzyme catalysis and transcriptional regulation.
Claiborne
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Department of Biochemistry, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.
Miller
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H
Parsonage
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Ross
R P
RP
D002384:Catalysis; D003545:Cysteine / Q000378:metabolism; D013293:Enterococcus faecalis / Q000201:enzymology; D004795:Enzyme Stability; D015971:Gene Expression Regulation, Enzymologic; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D013434:Sulfenic Acids / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D009097:Multienzyme Complexes; D013434:Sulfenic Acids; D014157:Transcription Factors; D010544:Peroxidases; C021845:NAD+ peroxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D003545:Cysteine