Electron tunneling through proteins

History 342 2. Activation barriers 343 2.1 Redox potentials 344 2.2 Reorganization energy 344 3. Electronic coupling 345 4. Ru-modified proteins 348 4.1 Reorganization energy 349 4.1.1 Cyt c 349 4.1.2 Azurin 350 4.2 Tunneling timetables 352 5. Multistep tunneling 357 6. Protein–protein reactions 359 6.1 Hemoglobin (Hb) hybrids 359 6.2 Cyt c /cyt b 5 complexes 360 6.3 Cyt c /cyt c peroxidase complexes 360 6.4 Zn–cyt c /Fe–cyt c crystals 361 7. Photosynthesis and respiration 362 7.1 Photosynthetic reaction centers (PRCs) 362 7.2 Cyt c oxidase (CcO) 364 8. Concluding remarks 365 9. Acknowledgments 366 10. References 366 Electron transfer processes are vital elements of energy transduction pathways in living cells. More than a half century of research has produced a remarkably detailed understanding of the factors that regulate these ‘currents of life’. We review investigations of Ru-modified proteins that have delineated the distance- and driving-force dependences of intra-protein electron-transfer rates. We also discuss electron transfer across protein–protein interfaces that has been probed both in solution and in structurally characterized crystals. It is now clear that electrons tunnel between sites in biological redox chains, and that protein structures tune thermodynamic properties and electronic coupling interactions to facilitate these reactions. Our work has produced an experimentally validated timetable for electron tunneling across specified distances in proteins. Many electron tunneling rates in cytochrome c oxidase and photosynthetic reaction centers agree well with timetable predictions, indicating that the natural reactions are highly optimized, both in terms of thermodynamics and electronic coupling. The rates of some reactions, however, significantly exceed timetable predictions; it is likely that multistep tunneling is responsible for these anomalously rapid charge transfer events.