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J.Csbj.2020.12.004 This document is downloaded from the VTT’s Research Information Portal https://cris.vtt.fi VTT Technical Research Centre of Finland Molecular mechanisms of electron transfer employed by native proteins and biological-inorganic hybrid systems Lienemann, Michael Published in: Computational and Structural Biotechnology Journal DOI: 10.1016/j.csbj.2020.12.004 Published: 01/01/2021 Document Version Publisher's final version License CC BY Link to publication Please cite the original version: Lienemann, M. (2021). Molecular mechanisms of electron transfer employed by native proteins and biological- inorganic hybrid systems. Computational and Structural Biotechnology Journal, 19, 206-213. https://doi.org/10.1016/j.csbj.2020.12.004 VTT By using VTT’s Research Information Portal you are bound by the http://www.vtt.fi following Terms & Conditions. P.O. box 1000FI-02044 VTT I have read and I understand the following statement: Finland This document is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of this document is not permitted, except duplication for research use or educational purposes in electronic or print form. You must obtain permission for any other use. Electronic or print copies may not be offered for sale. Download date: 03. Oct. 2021 Computational and Structural Biotechnology Journal 19 (2021) 206–213 journal homepage: www.elsevier.com/locate/csbj Molecular mechanisms of electron transfer employed by native proteins and biological-inorganic hybrid systems Michael Lienemann VTT Technical Research Centre of Finland Ltd., 02150 Espoo, Finland article info abstract Article history: Recent advances in enzymatic electrosynthesis of desired chemicals in biological-inorganic hybrid sys- Received 15 September 2020 tems has generated interest because it can use renewable energy inputs and employs highly specific cat- Received in revised form 3 December 2020 alysts that are active at ambient conditions. However, the development of such innovative processes is Accepted 5 December 2020 currently limited by a deficient understanding of the molecular mechanisms involved in electrode- Available online 14 December 2020 based electron transfer and biocatalysis. Mechanistic studies of non-electrosynthetic electron transfer- ring proteins have provided a fundamental understanding of the processes that take place during enzy- Keywords: matic electrosynthesis. Thus, they may help explain how redox proteins stringently control the reduction Electron transfer potential of the transferred electron and efficiently transfer it to a specific electron acceptor. The redox Electron bifurcation Redox potential sites at which electron donor oxidation and electron acceptor reduction take place are typically located Redox protein in distant regions of the redox protein complex and are electrically connected by an array of closely Enzymatic electrosynthesis spaced cofactors. These groups function as electron relay centers and are shielded from the surrounding Protein engineering environment by the electrically insulating apoporotein. In this matrix, electrons travel via electron tun- neling, i.e. hopping between neighboring cofactors, over impressive distances of upto several nanometers and, as in the case of the Shewanella oneidensis Mtr electron conduit, traverse the bacterial cell wall to extracellular electron acceptors such as solid ferrihydrite. Here, the biochemical strategies of protein- based electron transfer are presented in order to provide a basis for future studies on the basis of which a more comprehensive understanding of the structural biology of enzymatic electrosynthesis may be attained. Ó 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/). Contents 1. Introduction . ...................................................................................................... 206 2. Microbial electron transfer systems . ................................................................................... 208 2.1. Nitrogen reduction to ammonia by the Azotobacter vinelandii Mo-nitrogenase . ................................... 208 2.2. Electron transfer by multiheme cytochromes c........................................................................ 208 2.3. Flavin-based electron bifurcation in the NADH-dependent ferredoxin:NADP reductase Nfn. ................................... 210 3. Concluding remarks . ................................................................................... 211 Declaration of Competing Interest . ................................................................................... 211 Acknowledgements . ................................................................................... 211 References . ...................................................................................................... 211 1. Introduction its environment. These reactions are catalyzed by enzymes and power other reactions that ensure the survival and propagation Survival of each biological species is highly dependent on its of the cell. Instrumental in this process are electron transfers ability to harness the energy contained in the chemical bonds in between intracellular and extracellular compounds, which has https://doi.org/10.1016/j.csbj.2020.12.004 2001-0370/Ó 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). M. Lienemann Computational and Structural Biotechnology Journal 19 (2021) 206–213 Fig. 1. Electron transfer in the apoproteins presented in this review is mediated by various cofactors including the covalently bound iron-sulfur clusters [2Fe-2S] (A) and [4Fe- 4S] (B), the P-cluster (C), FeMo cofactor (FeMo-co; D), heme c (E) as well as the non-covalently bound flavin adenine dinucleotide (FAD; F). Amino acids contributing to the covalent cofactor attachment to the apoprotein are shown in grey. Catalytically active iron atoms are colored blue and FAD nitrogen atoms transferring electrons during electron bifurcations are displayed in red. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) been fittingly captured by Nobel Prize-winning physiologist Albert experimentally by J. R. Winkler and H. B. Gray. They designed a Szent-Györgyi in his famous quote ‘‘Life is nothing but an electron photochemical system consisting of a photoactive Ru complex as looking for a place to rest”. As with most biochemical processes, redox center that is covalently bound to the surface of a cyto- electron transfer inside proteins is an electron tunneling reaction chrome or a blue copper protein [6,7]. By systematic variation of during which the electron hops from one electron relaying redox the position of Ru complex attachment, they were able to estimate center to another, in a stepping stone fashion, until it is transferred HDA and k, and determine the pathways along which electrons tra- to an external electron acceptor (cofactors discussed in this review vel between the redox centers [8,9]. In the case of electron transfer as redox centers are presented in Fig. 1). A theoretical framework within proteins, edge-to-edge distances between two individual for electron transfer is provided by the Marcus theory with which redox centers do not typically exceed 14 Å thereby ensuring that tunneling rates can be directly predicted for a wide range of reac- electron tunneling rates are faster than the common millisecond tions [1,2]. According to this theory, the rate of electron transfer bond-breaking at the active sites of enzymes [10]. depends on five parameters, i.e., the free reaction energy, DG0, According to a recent survey, iron sulfur clusters and hemes are the free activation energy, DGà, the reorganization energy, k, the the most common electron-transferring cofactors in proteins [10], electronic coupling of the electron donor–acceptor pair, HDA, and within which these are arranged as precisely spaced arrays that are the temperature. HDA is a measure of the probability at which elec- shielded from the surrounding aqueous environment by an insu- tron tunneling occurs between degenerate states of the donor and lating protein matrix [11]. Electron transfer by proteins was ini- acceptor. A large HDA is characteristic for an adiabatic electron tially described for the four membrane complexes of the transfer with a low energy barrier DGà when compared to non- mitochondrial respiratory chain that transfers two electrons from adiabatic (low HDA) electron transfers and strong coupling between the reduction equivalents NADH and succinate to a terminal elec- the nuclei and electron motion. DG0 is directly determined by the tron acceptor, such as oxygen, using a set of different redox cofac- redox potentials of the electron donor–acceptor couple, while k is tors including flavins, iron sulfur clusters and hemes [12]. The the energy required to reorganize the nuclei of the surrounding latter two are employed by Complex III and will be discussed in physical medium and increases with donor–acceptor separation. this minireview to illustrate the principles of electron bifurcation. In agreement with the Marcus theory, it was demonstrated by M. The possibility of driving enzyme reactions by
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