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Abstract The degree by which metalloproteins partially regulate net charge (Z) upon electron transfer (ET) was recently measured for the first time using “protein charge ladders” of azurin, cytochrome c, and myoglobin [Angew. Chem. Int. Ed.2018,57(19), 5364–5368;Angew. Chem.2018,130, 5462–5466]. Here, we show that Cu, Zn superoxide dismutase (SOD1) is unique among proteins in its ability to resist changes in net charge upon single ET (e.g., ΔZET(SOD1)=0.05±0.08 per electron, compared to ΔZET(Cyt‐c)=1.19±0.02). This total regulation of net charge by SOD1 is attributed to the protonation of the bridging histidine upon copper reduction, yielding redox centers that are isoelectric at both copper oxidation states. Charge regulation by SOD1 would prevent long range coulombic perturbations to residue pKa’s upon ET at copper, allowing SOD1’s “electrostatic loop” to attract superoxide with equal affinity (at both redox states of copper) during diffusion‐limited reduction and oxidation of superoxide.
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This content will become publicly available on March 1, 2026
Cytochromes P460 and c′-β: exploiting a novel fold for multiple functions
Abstract Two related classes of ligand-binding hemec-containing proteins with a high degree of structural homology have been identified and characterized over recent decades: cytochromes P460 (cyts P460), defined by an unusual heme-lysine cross-link, and cytochromesc′-β (cytsc′-β), containing a canonicalc-heme without the lysine cross-link. The shared protein fold of the cyt P460-cytc′-β superfamily can accommodate a variety of heme environments with entirely different reactivities. On the one hand, cyts P460 with polar distal pockets have been shown to oxidize NH2OH to NO and/or N2O via proton-coupled electron transfer. On the other hand, cytsc′-β with hydrophobic distal pockets have a proposed gas binding function similar to the unrelated, but more extensively characterized, alpha helical cytochromesc′. Recent studies have also identified ‘halfway house’ proteins (cyts P460 with non-polar heme pockets and cytsc′-β with polar distal heme pockets) with functions yet to be resolved. Here, we review the structural, spectroscopic and enzymatic properties of the cyt P460-cytc′-β superfamily with a view to understanding the structural determinants of their different functional properties. Graphical abstract
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- Award ID(s):
- 1921670
- PAR ID:
- 10615536
- Publisher / Repository:
- Springer
- Date Published:
- Journal Name:
- JBIC Journal of Biological Inorganic Chemistry
- Volume:
- 30
- Issue:
- 2
- ISSN:
- 1432-1327
- Page Range / eLocation ID:
- 181 to 207
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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