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Updated: May 16, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes
Divyansh Prakash1,2, Suchitra Mitra1,3, Simran Sony1
1Department of Chemistry and Biochemistry, University of Mississippi, University, MS, USA.
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.
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