pH-Induced Rotation of Lidless Lipase LipA from Bacillus subtilis at Lipase-Detergent Interface

Lipases exhibit a unique process during the catalysis of the hydrolysis of triglyceride substrates called interfacial activation. Surfactants are used as cosolvents with water not only to offer a less polar environment to the lipases needed for their interfacial activation but also to solvate the substrate which are poorly soluble in water. However, the presence of detergent in the medium can affect both the lipase and the substrate, making the construction of a microkinetic model for lipase activity in the presence of the detergent difficult. Herein, we study the interfacial activation of a lidless lipase LipA from Bacillus subtilis using extensive atomistic molecular dynamics simulations at different concentrations of the surfactant, Thesit (C12E8), at two pH values. Residues which bind to the monomeric detergent are found to be the same as the ones which have been reported earlier to bind to the substrate. Very importantly, a pH-induced rotation of the enzyme with respect to surfactant aggregate has been observed which not only explains the experimentally observed pH-dependent enzymatic activity of this lidless lipase, but also suggests its reorientation at an aqueous-lipodophilic interface.