Lipase Dynamics And Activation: The Case Of M37

Interfacial enzymes, such as lipases, have evolved to function at the dynamic interface between hydrophobic molecules and aqueous solution. These interfaces affect the catalytic behaviour exhibited by interfacial enzymes and, in the case of lipases, can often lead to structural transitions that are coupled to changes in enzyme activity. This process of surface-activation results in a dramatic increase in enzyme activity, often linked with interactions between the lipase and the interface. Understanding the mechanism and extent to which the enzyme binds to, interacts with, and is activated by an interface however remains unclear, as this may vary depending on the lipase and the interface in question.Here, we present a multi-scale computational investigation of how different interfaces affect the conformational dynamics of the psychrophilic lipase M37 (Ryu et al, 2005). This enzyme exhibits a unique catalytic profile with a very low activation energy towards short-chain triglycerides, and exhibits a superior stability in biodiesel production studies.Coarse-grained and atomistic molecular dynamics (MD) simulations are employed to study how this lipase interacts with biological membrane surfaces and a natural substrate interface. Our results reveal a potential activation pathway leading to an open form of the M37 lipase, which is further tested using steered MD simulations. Importantly, we also show that the resultant enzyme structure is able to bind substrates unimpeded, thus indicating that our obtained M37 structure is in a fully active or ‘open’ state. This open structure of M37 can thus be used in further investigation to optimise stability of the catalytically active state and improve product turnover, making M37 an attractive candidate for biotechnological applications.Reference:Ryu, H.S., Kim, H.K., Choi, W.C., Kim, H.M., Park, S.Y., Han, N.S., Oh, T.K., Lee, J.K. (2005) Applied microbiology biotechnology. 70: 321-326