Control of proton and electron transfer in de novo designed, biomimetic β hairpins

Tyrosine side chains are involved in proton coupled electron transfer reactions (PCET) in many complex proteins, including photosystem II (PSII) and ribonucleotide reductase. For example, PSII contains two redox-active tyrosines, TyrD (Y160D2) and TyrZ (Y161D1), which have different protein environments, midpoint potentials, and roles in catalysis. TyrD has a midpoint potential lower than that of TyrZ, and its protein environment is distinguished by potential π-cation interactions with arginine residues. Designed biomimetic peptides provide a system that can be used to investigate how the protein matrix controls PCET reactions. As a model for the redox-active tyrosines in PSII, we are employing a designed, 18 amino acid β hairpin peptide in which PCET reactions occur between a tyrosine (Tyr5) and a cross-strand histidine (His14). In this peptide, the single tyrosine is hydrogen-bonded to an arginine residue, Arg16, and a second arginine, Arg12, has a π-cation interaction with Tyr5. In this report, the effect of these hydrogen bonding and electrostatic interactions on the PCET reactions is investigated. Electrochemical titrations show that histidine substitutions change the nature of PCET reactions, and optical titrations show that Arg16 substitution changes the pK of Tyr5. Removal of Arg16 or Arg12 increases the midpoint potential for tyrosine oxidation. The effects of Arg12 substitution are consistent with the midpoint potential difference, which is observed for the PSII redox-active tyrosine residues. Our results demonstrate that a π-cation interaction, hydrogen bonding, and PCET reactions alter redox-active tyrosine function. These interactions can contribute equally to the control of midpoint potential and reaction rate.