Probing the nature of substrate binding in Humicola lanuginosa lipase through X-ray crystallography and intuitive modelling.

The catalytic triad of the neutral lipase from Humicola lanuginosa is buried by a short helix under aqueous conditions rendering the enzyme inactive. Upon adsorption to a lipid substrate interface this helix is displaced, thereby exposing the active site (interfacial activation). By covalently linking inhibitors to the active serine, it is possible to crystallize the enzyme in an interfacially activated state. Two such structures are reported here which mimic the tetrahedral transition states of lipolysis. To date, no crystal structures of a lipase--triglyceride complex exist for this enzyme. Therefore, possible interactions between this lipase and its substrate have been analysed through molecular modelling.