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Natural engineering principles of electron tunnelling in biological oxidation–reduction

Abstract

We have surveyed proteins with known atomic structure whose function involves electron transfer; in these, electrons can travel up to 14 Å between redox centres through the protein medium. Transfer over longer distances always involves a chain of cofactors. This redox centre proximity alone is sufficient to allow tunnelling of electrons at rates far faster than the substrate redox reactions it supports. Consequently, there has been no necessity for proteins to evolve optimized routes between redox centres. Instead, simple geometry enables rapid tunnelling to high-energy intermediate states. This greatly simplifies any analysis of redox protein mechanisms and challenges the need to postulate mechanisms of superexchange through redox centres or the maintenance of charge neutrality when investigating electron-transfer reactions. Such tunnelling also allows sequential electron transfer in catalytic sites to surmount radical transition states without involving the movement of hydride ions, as is generally assumed. The 14 Å or less spacing of redox centres provides highly robust engineering for electron transfer, and may reflect selection against designs that have proved more vulnerable to mutations during the course of evolution.

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Figure 1: Electron-transfer rates and statistics for natural multiredox centre oxidoreductase structures in the PDB as of February 1999.
Figure 2: Chains of redox centres are used to cover large distances in natural proteins; chains often include conspicuously exergonic and endergonic electron-transfer steps.
Figure 3: The proximity between redox centres in clusters allows rapid tunnelling access to considerably endergonic radical intermediate states.

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Acknowledgements

This work was supported by grants from the NIH. We are grateful to C. A. Wraight, G. T. Babcock, W. Junge, R. J. P. Williams and H. B. Gray for timely encouragement and insight. Several crystallographers, most notably H. Michel, M. Frey, D. Rees, E. Berry and R. Huber, gave us crystal coordinates before publication.

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Correspondence to P. Leslie Dutton.

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Page, C., Moser, C., Chen, X. et al. Natural engineering principles of electron tunnelling in biological oxidation–reduction. Nature 402, 47–52 (1999). https://doi.org/10.1038/46972

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