DMSO enhanced conformational switch of an interfacial enzyme.

Abstract

Interfacial proteins function in unique heterogeneous solvent environments, such as water-oil interfaces. One important example is microbial lipase, which is activated in an oil-water emulsion phase and has many important enzymatic functions. A unique aprotic dipolar organic solvent, dimethyl sulfoxide (DMSO), has been shown to increase the activity of lipases, but the mechanism behind this enhancement is still unknown. Here, all-atom molecular dynamics simulations of lipase in a binary solution were performed to examine the effects of DMSO on the dynamics of the gating mechanism. The amphiphilic α5 region of the lipase was a focal point for the analysis, since the structural ordering of α5 has been shown to be important for gating under other perturbations. Compared to the closed-gorge ensemble in an aqueous environment, the conformational ensemble shifts towards open-gorge structures in the presence of DMSO solvents. Increased width of the access channel is particularly prevalent in 45% and 60% DMSO concentrations (w/w). As the amount of DMSO increases, the α5 region of the lipase becomes more α-helical, as we previously observed in studies that address water-oil interfacial and high pressure activation. We believe that the structural ordering of α5 plays an essential role on gating and lipase activity.