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Computational studies of electron transfer in the bacterial deca-heme cytochrome MtrF

Breuer, M; (2015) Computational studies of electron transfer in the bacterial deca-heme cytochrome MtrF. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Certain bacteria possess the remarkable ability to respire on extracellular solid metal oxides, which requires a unique biomolecular machinery optimized for long-range electron transport. To perform this function efficiently, microorganisms have adapted multi-heme c-type cytochromes to arrange heme cofactors into wires that cooperatively span the cellular envelope, transmitting electrons along distances greater than 100 Å before they are passed on to extracellular terminal acceptors via direct contact or secreted soluble electron shuttles (like flavins). While the interactions and “whole-protein” properties of these special multi-heme proteins have been the subject of intensive research efforts, molecular-level insight has long been elusive. Here, a wide range of computational methods is deployed to study the electron transfer (ET) properties of outer membrane (OM)-associated decaheme cytochromes in the bacterium S. oneidensis, from explicit electronic structure calculations to empirical ligand docking. In particular, thermodynamic and kinetic parameters for heme-to-heme ET in the OM deca-heme cytochrome MtrF are calculated which enables us to model through-protein steady-state electron transport. Furthermore, the interaction of its homologue MtrC with the soluble shuttle flavin mononucleotide is studied via docking simulations. Our calculations of heme redox potentials in MtrF yielded a free energy surface with two “up-hill” steps of 0.2 eV for through-protein electron transport. These potential kinetic obstacles were found to be counteracted by stronger electronic interactions precisely between those cofactors that form the free energy hills. This correlation of thermodynamic properties and electronic interactions was found to be essential for the cytochrome to yield through-protein electron transport rates of 104-105 s−1 (as determined from our steady-state electron transport calculations), consistent with an experimentally established lower limit. Our docking studies reproduce an experimentally determined affinity quite well and are consistent with the existing hypothesis regarding the role of flavin molecules as electron shuttles; they furthermore suggest concrete binding sites on the deca-heme cytochrome MtrC. Overall, by deploying and combining a range of computational approaches, this work has yielded molecular-level insights intoOMdeca-heme cytochromes that are difficult to obtain from experiment.

Type: Thesis (Doctoral)
Title: Computational studies of electron transfer in the bacterial deca-heme cytochrome MtrF
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1470096
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