Jay R. Winkler: Electrons, Holes, and Proteins
Director of the Beckman Institute Laser Resource Center at the California Institute of Technology
Biological electron transfers often occur between metal-containing cofactors that are separated by very large molecular distances.
Employing photosensitizer-modified iron and copper proteins, we have shown that single-step electron tunneling can occur on nanosecond to microsecond timescales over distances between 15 and 20 angstroms. We also have shown that charge transport can occur over even longer distances by hole hopping (multistep tunneling) through intervening tyrosines and tryptophans. Indeed, functional radical transfer pathways comprised of tyrosine and tryptophan residues have been identified in several enzymes, including ribonucleotide reductase, photosystem II, DNA photolyase, and MauG.
Many metalloenzymes catalyze vital biological transformations involving the incorporation of one (monooxygenases) or two (dioxygenases) O-atoms from molecular oxygen into organic substrates. These enzymes coordinate the delivery of protons and electrons to O2 to generate powerful active-site metallo-oxidants that react with substrates. In the event that a suitable substrate is not available, tyrosine and tryptophan redox chains can protect the enzyme by delivering active-site redox holes to the protein surface where they will be scavenged by solution reductants. Analysis of structures in the Protein Data Bank reveals that oxygenases and dioxygenases often contain chains of two or more redox-active residues (metal cofactors, tyrosines, tryptophans) separated by less than 5 angstroms. It is possible that hole hopping through radical transfer chains protects these enzymes when normal substrate turnover is disrupted.