Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes
Abstract Metalloenzymes play essential roles in biology. However, unraveling how outer-sphere interactions can be predictably controlled to influence their functions remains a significant challenge. Inspired by Cu enzymes, we demonstrate how variations in the primary, secondary, and outer coordinati...
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| Format: | Article |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57904-5 |
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| author | Divyansh Prakash Suchitra Mitra Simran Sony Morgan Murphy Babak Andi Landon Ashley Pallavi Prasad Saumen Chakraborty |
| author_facet | Divyansh Prakash Suchitra Mitra Simran Sony Morgan Murphy Babak Andi Landon Ashley Pallavi Prasad Saumen Chakraborty |
| author_sort | Divyansh Prakash |
| collection | DOAJ |
| description | Abstract Metalloenzymes play essential roles in biology. However, unraveling how outer-sphere interactions can be predictably controlled to influence their functions remains a significant challenge. Inspired by Cu enzymes, we demonstrate how variations in the primary, secondary, and outer coordination-sphere interactions of de novo designed artificial copper proteins (ArCuPs) within trimeric (3SCC) and tetrameric (4SCC) self-assemblies—featuring a trigonal Cu(His)3 and a square pyramidal Cu(His)4(OH2) coordination—influence their catalytic and electron transfer properties. While 3SCC electrocatalyzes C-H oxidation, 4SCC does not. CuI-3SCC reacts more rapidly with H2O2 than O2, whereas 4SCC is less active. Electron transfer, reorganization energies, and extended H2O-mediated hydrogen bonding patterns provide insights into the observed reactivity differences. The inactivity of 4SCC is attributed to a significant solvent reorganization energy barrier mediated by a specific His---Glu hydrogen bond. When this hydrogen bond is disrupted, the solvent reorganization energy is reduced, and C-H peroxidation activity is restored. |
| format | Article |
| id | doaj-art-dec1a4bda6964debb3e055f14bdad8a4 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dec1a4bda6964debb3e055f14bdad8a42025-08-20T02:10:13ZengNature PortfolioNature Communications2041-17232025-03-0116111310.1038/s41467-025-57904-5Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymesDivyansh Prakash0Suchitra Mitra1Simran Sony2Morgan Murphy3Babak Andi4Landon Ashley5Pallavi Prasad6Saumen Chakraborty7Department of Chemistry and Biochemistry, University of MississippiDepartment of Chemistry and Biochemistry, University of MississippiDepartment of Chemistry and Biochemistry, University of MississippiDepartment of Chemistry and Biochemistry, University of MississippiCenter for BioMolecular Structure, National Synchrotron Light Source II, Brookhaven National LaboratoryDepartment of Chemistry and Biochemistry, University of MississippiDepartment of Chemistry and Biochemistry, University of MississippiDepartment of Chemistry and Biochemistry, University of MississippiAbstract Metalloenzymes play essential roles in biology. However, unraveling how outer-sphere interactions can be predictably controlled to influence their functions remains a significant challenge. Inspired by Cu enzymes, we demonstrate how variations in the primary, secondary, and outer coordination-sphere interactions of de novo designed artificial copper proteins (ArCuPs) within trimeric (3SCC) and tetrameric (4SCC) self-assemblies—featuring a trigonal Cu(His)3 and a square pyramidal Cu(His)4(OH2) coordination—influence their catalytic and electron transfer properties. While 3SCC electrocatalyzes C-H oxidation, 4SCC does not. CuI-3SCC reacts more rapidly with H2O2 than O2, whereas 4SCC is less active. Electron transfer, reorganization energies, and extended H2O-mediated hydrogen bonding patterns provide insights into the observed reactivity differences. The inactivity of 4SCC is attributed to a significant solvent reorganization energy barrier mediated by a specific His---Glu hydrogen bond. When this hydrogen bond is disrupted, the solvent reorganization energy is reduced, and C-H peroxidation activity is restored.https://doi.org/10.1038/s41467-025-57904-5 |
| spellingShingle | Divyansh Prakash Suchitra Mitra Simran Sony Morgan Murphy Babak Andi Landon Ashley Pallavi Prasad Saumen Chakraborty Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes Nature Communications |
| title | Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes |
| title_full | Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes |
| title_fullStr | Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes |
| title_full_unstemmed | Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes |
| title_short | Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes |
| title_sort | controlling outer sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes |
| url | https://doi.org/10.1038/s41467-025-57904-5 |
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