Engineering a Functional Histidine Brace Copper-Binding Site into a <i>De Novo</i>-Designed Protein Scaffold.

ABSTRACT: De novo metalloprotein design has contributed to tremendous advances in bioinorganic chemistry by allowing the manufacturing of proteins with unique structures and functionalities that go beyond evolutionary constraints. Among the array of metal sites that can be engineered within de novo scaffolds, the design of catalytic copper centers is particularly challenging but still harder to achieve due to the versatile coordination environment and redox properties of the copper ion. Here, we present miniLPMO, a fully de novo protein, incorporating a functional histidine brace copper-binding site. Starting from a four-helix-bundle scaffold based on the designed homodimeric α₂D protein, our design has integrated rational and computational strategies to optimize coor

SUBMITTER: La Gatta S 

PROVIDER: S-EPMC12569686 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature