Electrons, holes, protons, and proteins

Abstract

Most biol. redox transformations involve reagents with formal potentials in the ±1 V vs. NHE range. At the periphery of this potential window, proteins present a decidedly unsym. medium for electron transfer (ET). Whereas redn. of peptides and small arom. groups only proceeds at potentials more neg. than -2.5 V vs. NHE, one-electron oxidns. of arom. and sulfur-contg. amino-acids, as well as the peptide backbone itself, can occur at potentials in the 1.0-1.5 V vs. NHE range. This asymmetry suggests that proteins are superexchange mediators of ET in reactions of low-potential redox couples, but in high-potential redox transformations, proteins can support multistep tunneling (hopping). The sidechains of tyrosine (Tyr) and tryptophan (Trp) residues generate acidic radical cations upon oxidn. at high potentials, and several enzymes are known to utilize Tyr and Trp radicals in their catalytic mechanisms. Precise positioning of Tyr and Trp sidechains, and suitable proton acceptors, is required to provide effective redox function. A search of the protein structural database reveals that about one third of all proteins contain Tyr/Trp chains composed of three or more residues. Although these chains are distributed among all enzyme classes, they appear with greatest frequency in the oxidoreductases and hydrolases. Approx. half of the dioxygen-utilizing oxidoreductases have Tyr/Trp chain lengths of three or more residues. Our current efforts are aimed at elucidating the roles of Tyr and Trp radicals in the redox chem. of heme oxgenases and multicopper oxidases.

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