PROBING THE NATURE OF SUBSTRATE-BINDING IN HUMICOLA-LANUGINOSA LIPASETHROUGH X-RAY CRYSTALLOGRAPHY AND INTUITIVE MODELING

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 su ch structures are reported here which mimic the tetrahedral transition states of lipolysis. To date, no crystal structures of a lipase-trigl yceride complex exist for this enzyme. Therefore, possible interaction s between this lipase and its substrate have been analysed through mol ecular modelling.