title: 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.
authors.affiliation: UT-ORNL Graduate School of Genome Science and Technology, Knoxville, TN, 37996.|Oak Ridge National Laboratory, Center for Molecular Biophysics, Oak Ridge, TN, 37830.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lindsay
authors.affiliation: Oak Ridge National Laboratory, Center for Molecular Biophysics, Oak Ridge, TN, 37830.|National Institute for Mathematical and Biological Synthesis, Knoxville, TN, 37996.
authors.forename: Quentin R
authors.initials: QR
authors.lastname: Johnson
authors.affiliation: Oak Ridge National Laboratory, Center for Molecular Biophysics, Oak Ridge, TN, 37830.|Department of Biochemistry and Cellular & Molecular Biology, University of Tennessee, Knoxville, TN, 37996.
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Evangelista
authors.affiliation: Institute of Chemistry, University of the Philippines Diliman, Quezon City, Philippines.
authors.forename: Ricky B
authors.initials: RB
authors.lastname: Nellas
authors.affiliation: Oak Ridge National Laboratory, Center for Molecular Biophysics, Oak Ridge, TN, 37830. tshen@utk.edu.|Department of Biochemistry and Cellular & Molecular Biology, University of Tennessee, Knoxville, TN, 37996. tshen@utk.edu.
authors.forename: Tongye
authors.initials: T
authors.lastname: Shen
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry*; D000072417:Protein Domains; D011550:Pseudomonas aeruginosa / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D008049:Lipase; D004121:Dimethyl Sulfoxide
keywords: DMSO; computer simulation; conformational switch; lipase; organic solvent