Protein-sulfenic acids: Diverse roles for an unlikely player in enzyme catalysis and redox regulation

While it has been known for more than 20 years that unusually stable cystei ne-sulfenic acid (Cys-SOH) derivatives can be introduced in selected protei ns by mild oxidation, only recently have chemical and crystallographic evid ence for functional Cys-SOH been presented with native proteins such as NAD H peroxidase and NADH oxidase, nitrile hydratase, and the hORF6 and AhpC pe roxiredoxins, In addition, Cys-SOH forms of protein tyrosine phosphatases a nd glutathione reductase have been suggested to play key roles in the rever sible inhibition of these enzymes during tyrosine phosphorylation-dependent signal transduction events and nitrosative stress, respectively, Substanti al chemical data have also been presented which implicate Cys-SOH in redox regulation of transcription factors such as Fos and Jun (activator protein- 1) and bovine papillomavirus-l E2 protein. Functionally, the Cys-SOHs in NA DH peroxidase, NADH oxidase, and the peroxiredoxins serve as either catalyt ically essential redox centers or transient intermediates during peroxide r eduction, In nitrile hydratase, the active-site Cys-SOH functions in both i ron coordination and NO binding but does not play any catalytic redox role. In Fos and Jun and the E2 protein, on the other hand, a key Cys-SH serves as a sensor for intracellular redox status; reversible oxidation to Cys-SOH as proposed inhibits the corresponding DNA binding activity. These functio nal Cys-SOHs have roles in diverse cellular processes, including signal tra nsduction, oxygen metabolism and the oxidative stress response, and transcr iptional regulation, as well as in the industrial production of acrylamide, and their detailed analyses are beginning to provide the chemical foundati on necessary for understanding protein-SOH stabilization and function.