Cysteine sulfenic acid as an intermediate in disulfide bond formation and nonenzymatic protein folding.
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 (O(2)) 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.
Rehder
Douglas S
DS
Molecular Biomarkers, The Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA.
Borges
Chad R
CR
D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013434:Sulfenic Acids / Q000737:chemistry* / Q000378:metabolism
D004220:Disulfides; D010455:Peptides; D013434:Sulfenic Acids; C100870:cysteinesulfenic acid; D003545:Cysteine