Cysteine sulfenic Acid as an Intermediate in Disulfide Bond Formation and Nonenzymatic Protein Folding

• Published in: Biochemistry (Easton) Vol. 49; no. 35; pp. 7748 - 7755
• Main Authors: Rehder, Douglas S, Borges, Chad R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.09.2010
• Subjects: Cysteine - analogs & derivatives; Cysteine - chemistry; Cysteine - metabolism; Dimerization; Disulfides - chemistry; Disulfides - metabolism; Oxidative Stress; Peptides - chemistry; Peptides - metabolism; Protein Folding; Protein Processing, Post-Translational; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sulfenic Acids - chemistry; Sulfenic Acids - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi1008694

As a posttranslational protein modification, cysteine sulfenic acid (Cys-SOH) is well established as an oxidative stress-induced mediator of enzyme function and redox signaling. Data presented herein show that protein Cys-SOH forms spontaneously in air-exposed aqueous solutions of unfolded (disulfide-reduced) protein in the absence of added oxidizing reagents, mediating the oxidative disulfide bond formation process key to in vitro, nonenzymatic protein folding. Molecular oxygen (O2) and trace metals [e.g., copper(II)] are shown to be important reagents in the oxidative refolding process. Cys-SOH is also shown to play a role in spontaneous disulfide-based dimerization of peptide molecules containing free cysteine residues. In total, the data presented expose a chemically ubiquitous role for Cys-SOH in solutions of free cysteine-containing protein exposed to air.