Molecular evolution of the pancreatic lipase and two related enzymes towards different substrate selectivities

The pancreatic lipase gene family includes lipoprotein lipases, hepatic lipases, pancreatic lipases, phospholipases Al from vespid venoms, and non-enzymatic proteins from Drosophila. Among the previous enzymes, the classical human pancreatic lipase (HPL), the guinea pig pancreatic lipase-related protein 2 (GPLRP2) and the phospholipase AI from hornet venom (DolmI) illustrate three steps in the molecular evolution of the pancreatic lipase gene family towards different substrate selectivities for triglycerides and phospholipids. Based on the known 3D structure of HPL, sequence alignments and kinetic properties, we compared these three enzymes for a better understanding of their structure-function relationships. Three surface loops surrounding the active site (beta 5 loop, beta 9 loop, lid domain) an believed to play an important role in substrate selectivity.