The electrochemical potentials of redox-active proteins need to be tuned accurately to the correct values for proper biological function. Here we describe a diheme cytochrome c with high heme redox potentials of about +350 mV, despite having a large overall negative charge which typically reduces redox potentials. High resolution crystal structures, spectroelectrochemical measurements and high-end computational methods show how this is achieved: each heme iron has a calcium cation positioned next to it at a distance of only 6.9 Å, raising their redox potentials by several hundred mV through electrostatic interaction. We suggest that this has evolved to provide the protein with a high redox potential despite its large negative surface charge, which it likely requires for interactions with redox partners.
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| http://dx.doi.org/10.1016/j.jbc.2024.108082 | DOI Listing |
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