Exploring Crystallographic Interactions between MOFs and Proteins: Toward a Breakthrough in Artificial Enzyme Mechanisms

This proposal aims to explore interactions between Artificial Enzyme (AE) Metal-Organic Frameworks (MOFs) and proteins using synchrotron single-crystal X-ray diffraction tailored for small molecules. By controlling both formation and interpenetration, AE MOFs with diverse pore sizes and multifunctional metal clusters/ligands have been synthesized. Acting as reactor-like catalysts, these MOFs achieve protein unfolding within 24 hours at 60 °C and complete hydrolysis in 3-6 days. However, the underlying mechanism remains unclear due to the challenges in understanding protein-MOF interactions. To elucidate this, MOF-protein co-crystals were prepared as direct evidence, necessitating the use of high-resolution small molecule beamline to obtain detailed structures. High-quality crystallographic data can confirm where the protein interacts with MOF cavities and determine the absolute structure of MOF-protein co-crystals, revealing the active sites (Scheme 1).