Chiral Substrate Binding Induced Dynamic Restructuring of Binuclear Copper Centers for Enzyme-Like Catalysis

Binuclear copper centers as critical catalytic cores in metalloenzymes, enabling stereoselective reactions through precisely ordered protein structures. However, limited understanding of dynamic substrate recognition and its interaction with catalytic centers has hindered the replication of these sophisticated functions in synthetic systems. In this study, we introduce a breakthrough approach using the natural dipeptide carnosine to construct structurally adaptive binuclear copper centers, effectively mimicking the plasticity of natural metalloenzymes. Through state-of-the-art two-dimensional infrared spectroscopy, we reveal a novel stereoselectivity mechanism that extends beyond the classical "induced-fit" model, demonstrating chiral substrate induced restructuring of the binuclear copper centers. These findings provide fundamental insights into metalloenzyme catalysis and establish a practical design platform for developing high-performance biocatalysts, with promising applications in green chemical synthesis and sustainable industrial processes.