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Strand-swapped SH3 domain dimer with superoxide dismutase activity

The design of metalloproteins allows us to better understand metal complexation in proteins and the resulting function. In this study, we incorporated a Cu2+-binding site into a natural protein domain, the 58 amino acid c-Crk-SH3, to create a miniaturized superoxide dismutase model, termed SO1. The...

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Main Authors: Häge, Florian (Author) , Schwan, Merlin (Author) , Conde González, Marcos Rafael (Author) , Huber, Jonas (Author) , Germer, Stefan (Author) , Macrì, Matilde (Author) , Kopp, Jürgen (Author) , Sinning, Irmgard (Author) , Thomas, Franziska (Author)
Format: Article (Journal)
Language:English
Published: January 10, 2025
In: ACS central science
Year: 2025, Volume: 11, Issue: 1, Pages: 157-166
ISSN:2374-7951
DOI:10.1021/acscentsci.4c01347
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1021/acscentsci.4c01347
Verlag, kostenfrei, Volltext: https://pubs.acs.org/doi/10.1021/acscentsci.4c01347
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Author Notes:Florian R. Häge, Merlin Schwan, Marcos Rafael Conde González, Jonas Huber, Stefan Germer, Matilde Macrì, Jürgen Kopp, Irmgard Sinning, and Franziska Thomas
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Summary:The design of metalloproteins allows us to better understand metal complexation in proteins and the resulting function. In this study, we incorporated a Cu2+-binding site into a natural protein domain, the 58 amino acid c-Crk-SH3, to create a miniaturized superoxide dismutase model, termed SO1. The resulting low complexity metalloprotein was characterized for structure and function by circular dichroism and UV spectroscopy as well as EPR spectroscopy and X-ray crystallography. The miniprotein was found to be a strand-swapped dimer with an unusual coupled binuclear Type 2-like copper center in each protomer. SO1-Cu was found to be SOD-active with an activity only 1 order of magnitude lower than that of natural SOD enzymes and 1 to 2 orders of magnitude higher than that of other low-complexity SOD protein models of similar size. This serendipitous design provides us with a new structural template for future designs of binuclear metalloproteins with different metal ions and functions.
Item Description:Gesehen am 12.09.2025
Physical Description:Online Resource
ISSN:2374-7951
DOI:10.1021/acscentsci.4c01347

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