| Abstract
| - 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 sidechains. For these redox-active tyrosines, proton transfer couples with electron transfer, because the phenolicpKA of the tyrosine is altered by changes in the tyrosine redox state. To develop an experimentally tractablepeptide system in which the effect of proton and electron coupling can be investigated, we have designeda novel amino acid sequence that contains one tyrosine residue. The tyrosine can be oxidized by ultravioletphotolysis 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 betweenthe histidine and tyrosine side chains. The effect of the cross-strand interaction was probed by electronparamagnetic resonance and electrochemistry. The data are consistent with an increase in histidine pKAwhen the tyrosine is oxidized; the effect of this thermodynamic coupling is to increase tyrosyl radical yieldat low pH. The coupling mechanism is attributed to an interstrand π−cation interaction, which stabilizesthe tyrosyl radical. A similar interaction between histidine and tyrosine in enzymes provides a regulatorymechanism for enzymatic electron-transfer reactions.
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