Influence of protein interactions on oxidation/reduction midpoint potentials of cofactors in natural and de novo metalloproteins

As discussed throughout this special issue, oxidation and reduction reactions play critical roles in the function of many organisms. In photosynthetic organisms, the conversion of light energy drives oxidation and reduction reactions through the transfer of electrons and protons in order to create energy-rich compounds. These reactions occur in proteins such as cytochrome c, a heme-containing water-soluble protein, the bacteriochlorophyllcontaining reaction center, and photosystemIIwhere water is oxidized at the manganese cluster. A critical measure describing the ability of cofactors in proteins to participate in such reactions is the oxidation/reductionmidpoint potential. In this review, the basic concepts of oxidation/reduction reactions are reviewedwith a summary of the experimental approaches used tomeasure the midpoint potential of metal cofactors. For cofactors in proteins, the midpoint potential not only depends upon the specific chemical characteristics of cofactors but also upon interactions with the surrounding protein, such as the nature of the coordinating ligands and protein environment. These interactions can be tailored to optimize an oxidation/reduction reaction carried out by the protein. As examples, the midpoint potentials of hemes in cytochromes, bacteriochlorophylls in reaction centers, and the manganese cluster of photosystemII are discussedwith an emphasis on the influence that protein interactions have on these potentials. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems.