Ligand-dependent, single protein conformational transitions and manipulation

Using a high-resolution single-molecule nanocircuit approach, we observed that enzyme conformational states and transitions are influenced by the specific ligands. In the case of lysozyme interacting with peptidoglycan substrates, it exhibited dynamic transitions between open, intermediate, and fully closed, hydrolysis-ready conformational states with occasional interruptions. However, when interacting with substrate analogs, lysozyme underwent minimal conformational changes, transitioning from an open to a slightly closed, excited state with rapid transition rates. Furthermore, we investigated the potential impact of non-thermal noise on these conformational transitions and its role in enzyme specificity and catalytic activity.