Electron flow through biological molecules: does hole hopping protect proteins from oxidative damage?
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 at distances between 15 and 20 Å. We also have shown that charge transport can occur over even longer distances by hole hopping (multistep tunneling) through intervening tyrosines and tryptophans. In this perspective, we advance the hypothesis that such hole hopping through Tyr/Trp chains could protect oxygenase, dioxygenase, and peroxidase enzymes from oxidative damage. In support of this view, by examining the structures of P450 (CYP102A) and 2OG-Fe (TauD) enzymes, we have identified candidate Tyr/Trp chains that could transfer holes from uncoupled high-potential intermediates to reductants in contact with protein surface sites.
© 2015 Cambridge University Press 2015. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Published online: 16 July 2015. We thank Maraia Ener, Jeff Warren, Lionel Cheruzel, Kana Takematsu, and Oliver Shafaat for helpful discussions. Research reported in this publication was supported by The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number R01DK019038 to HBG and JRW. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Arnold and Mabel Beckman Foundation.
Published - S0033583515000062a.pdf
Accepted Version - nihms-765391.pdf