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Electron transfer and reaction mechanism of laccases

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Abstract

Laccases are part of the family of multicopper oxidases (MCOs), which couple the oxidation of substrates to the four electron reduction of O2 to H2O. MCOs contain a minimum of four Cu’s divided into Type 1 (T1), Type 2 (T2), and binuclear Type 3 (T3) Cu sites that are distinguished based on unique spectroscopic features. Substrate oxidation occurs near the T1, and electrons are transferred approximately 13 Å through the protein via the Cys-His pathway to the T2/T3 trinuclear copper cluster (TNC), where dioxygen reduction occurs. This review outlines the electron transfer (ET) process in laccases, and the mechanism of O2 reduction as elucidated through spectroscopic, kinetic, and computational data. Marcus theory is used to describe the relevant factors which impact ET rates including the driving force, reorganization energy, and electronic coupling matrix element. Then, the mechanism of O2 reaction is detailed with particular focus on the intermediates formed during the two 2e− reduction steps. The first 2e− step forms the peroxide intermediate, followed by the second 2e− step to form the native intermediate, which has been shown to be the catalytically relevant fully oxidized form of the enzyme.

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Acknowledgments

SMJ would like to thank Drs. Dave Heppner and Christian Kjaergaard for their contributions to this study and for many illuminating conversations on MCOs. EIS is indebted to all his past students and collaborators upon whose science this review is based. This research is supported by NIH Grant R01DK031450. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Chemistry, Stanford University, 333 Campus Drive, Stanford, CA, 94305, USA

    Stephen M. Jones & Edward I. Solomon

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  1. Stephen M. Jones
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  2. Edward I. Solomon
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Correspondence to Edward I. Solomon.

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Jones, S.M., Solomon, E.I. Electron transfer and reaction mechanism of laccases. Cell. Mol. Life Sci. 72, 869–883 (2015). https://doi.org/10.1007/s00018-014-1826-6

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