Structure and Function of Lipases

This chapter focuses on the current progress in crystallographic studies of neutral lipases and the impact of these studies have on understanding of the structure-function relationships in lipolytic enzymes. Lipid metabolism begins with a meal, and after a preliminary digestion in the stomach, the gastric contents are sprayed into the intestine where dietary lipids combine with the biliary secretion to form an emulsion providing a large lipid-aqueous interface where lipases may act. Triglyceride hydrolysis is accomplished principally by pancreatic lipase, which together with colipase, binds to the interface where it has access to the lipid. The three-dimensional structure of this enzyme as well as the structures of several fungal lipases is described. The structural basis of the enzymatic hydrolysis of the ester bond and activation of lipases at an oil/water interface is focused. Possible relationships between lipases and other serine hydrolases are discussed in the context of structural comparisons. The chapter also describes the currently available structural database and provides fascinating insights into the mechanism of interfacial activation and ester bond hydrolysis by this group of lipases.