8VHS

X-ray Structure of a De Novo Designed Self Assembled Peptide Tetramer Featuring a Cu(His)4(H2O) Coordination Motif

Summary for 8VHS

• Entry DOI: 10.2210/pdb8vhs/pdb
• Descriptor: Cu-4SCC, COPPER (II) ION (3 entities in total)
• Functional Keywords: de novo design; peptides; self-assembly; copper, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 4
• Total formula weight: 16118.36

Authors

Chakraborty, S.,Mitra, S.,Prakash, D.,Prasad, P. (deposition date: 2024-01-02, release date: 2025-04-16)

Primary citation

Prakash, D.,Mitra, S.,Sony, S.,Murphy, M.,Andi, B.,Ashley, L.,Prasad, P.,Chakraborty, S.
Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes.
Nat Commun, 16:3048-3048, 2025

PubMed 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) and a square pyramidal Cu(His)(OH) coordination-influence their catalytic and electron transfer properties. While 3SCC electrocatalyzes C-H oxidation, 4SCC does not. Cu-3SCC reacts more rapidly with HO than O, whereas 4SCC is less active. Electron transfer, reorganization energies, and extended HO-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.

PubMed: 40155633
DOI: 10.1038/s41467-025-57904-5

Experimental method

X-RAY DIFFRACTION (1.36 Å)