Issue 35, 2024

Proton-coupled electron transfer at a mis-metalated zinc site detected with protein charge ladders

Abstract

Distinguishing proton-coupled electron transfer (PCET) from uncoupled electron transfer (ET) in proteins can be challenging. A recent investigation [J. C. Koone, M. Simmang, D. L. Saenger, M. L. Hunsicker-Wang and B. F. Shaw, J. Am. Chem. Soc., 145, 16488–16497] reported that protein charge ladders and capillary electrophoresis can distinguish between single ET, PCET, and two-proton coupled ET (2PCET) by directly measuring the change in protein net charge upon reduction/oxidation (ΔZET). The current study used similar methods to assess PCET in zinc-free, “double copper” superoxide dismutase-1 (4Cu-SOD1), where one copper is bound at the copper site of each monomer and one copper is bound at the bridging zinc site, resulting in a quasi-type III Cu center. At pH 7.4, the net charge (Z) of the 4Cu-SOD1 dimer was unaffected by reduction of all four Cu2+ ions, i.e., ΔZ4ET = −0.09 ± 0.05 per dimer (−0.02 ± 0.01 per copper atom). These values suggest that PCET is taking place at all four Cu atoms of the homodimer. Molecular dynamics and Poisson–Boltzmann calculations suggest that a metal-coordinating histidine at the zinc site (His71) is the proton acceptor. These data show how ligands of a naturally occurring zinc site can help facilitate PCET when the right redox metal is bound.

Graphical abstract: Proton-coupled electron transfer at a mis-metalated zinc site detected with protein charge ladders

Supplementary files

Article information

Article type
Paper
Submitted
13 5月 2024
Accepted
12 8月 2024
First published
28 8月 2024
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2024,26, 22870-22881

Proton-coupled electron transfer at a mis-metalated zinc site detected with protein charge ladders

M. Gonzalez, M. J. Guberman-Pfeffer, J. C. Koone, C. M. Dashnaw, T. J. Lato and B. F. Shaw, Phys. Chem. Chem. Phys., 2024, 26, 22870 DOI: 10.1039/D4CP01989J

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