The Conformational Transitions and Dynamics of Lipase Regulated by Water-Oil Interfaces.

Structural dynamics and conformational transitions are crucial for the activities of enzymes. As one of the most widely used industrial biocatalysts, lipase could be activated by the water-oil interfaces. The interface activations were believed to be dominated by the close-to-open transitions of the lid subdomains. However, the detailed mechanism and the roles of structure transitions are still under debate. In this study, the dynamic structures and conformational transitions of lipase (LipA) were investigated by combining all-atom molecular dynamics simulations, enhanced sampling simulation, and spectrophotometric assay experiments. The conformational transitions between the lid-open and lid-closed states of LipA in aqueous solution are directly observed by the computational simulation methods. The interactions between the hydrophobic residues on the two lid-subdomains are the driven forces for the LipA closing. Meanwhile, the hydrophobic environment provided by the oil interfaces would separate the interactions between the lid-subdomains and promote the structure opening of LipA. Moreover, our studies demonstrate the opening of the lids structure is insufficient to initiate the interfacial activation, providing explanations for the inability of interfacial activation of many lipases with lid structures.