Proton-coupled electron-transfer reactions are central to enzymatic mechanism in many proteins. In several enzymes, essential electron-transfer reactions involve oxidation and reduction of tyrosine side chains. For these redox-active tyrosines, proton transfer couples with electron transfer, because the phenolic pKA of the tyrosine is altered by changes in the tyrosine redox state. To develop an experimentally tractable peptide system in which the effect of proton and electron coupling can be investigated, we have designed a novel amino acid sequence that contains one tyrosine residue. The tyrosine can be oxidized by ultraviolet photolysis or electrochemical methods and has a potential cross-strand interaction with a histidine residue. NMR spectroscopy shows that the peptide forms a β-hairpin with several interstrand dipolar contacts between the histidine and tyrosine side chains. The effect of the cross-strand interaction was probed by electron paramagnetic resonance and electrochemistry. The data are consistent with an increase in histidine pKA when the tyrosine is oxidized; the effect of this thermodynamic coupling is to increase tyrosyl radical yield at low pH. The coupling mechanism is attributed to an interstrand π-cation interaction, which stabilizes the tyrosyl radical. A similar interaction between histidine and tyrosine in enzymes provides a regulatory mechanism for enzymatic electron-transfer reactions.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of the American Chemical Society|
|State||Published - Apr 11 2007|