Willems_2017_Biochim.Biophys.Acta_1859_340

Lipases are enzymes of biotechnological importance that function at the interface formed between hydrophobic and aqueous environments. Hydrophobic interfaces can induce structural transitions in lipases that result in an increase in enzyme activity, although the detailed mechanism of this process is currently not well understood for many lipases. Here, we present a multi-scale molecular dynamics simulation study of how different interfaces affect the conformational dynamics of the psychrophilic lipase M37. Our simulations show that M37 lipase is able to interact both with anionic lipid bilayers and with triglyceride surfaces. Interfacial interactions with triglyceride surfaces promote large-scale motions of the lid region of M37, spanning residues 235-283, revealing an entry pathway to the catalytic site for substrates. Importantly, these results suggest a potential activation mechanism for M37 that deviates from other related enzymes, such as Thermomyces lanuginosus lipase. We also investigated substrate binding in M37 by using steered MD simulations, confirming the open state of this lipase. The exposure of hydrophobic residues within lid and active site flap regions (residues 94-110) during the activation process provides insights into the functional effect of hydrophobic surfaces on lipase activation.