MOLECULAR EVOLUTION OF THE PANCREATIC LIPASE AND 2 RELATED ENZYMES TOWARDS DIFFERENT SUBSTRATE SELECTIVITIES

The pancreatic lipase gene family includes lipoprotein lipases, hepati c lipases, pancreatic lipases, phospholipases Al from vespid venoms, a nd non-enzymatic proteins from Drosophila. Among the previous enzymes, the classical human pancreatic lipase (HPL), the guinea pig pancreati c lipase-related protein 2 (GPLRP2) and the phospholipase AI from horn et venom (DolmI) illustrate three steps in the molecular evolution of the pancreatic lipase gene family towards different substrate selectiv ities for triglycerides and phospholipids. Based on the known 3D struc ture of HPL, sequence alignments and kinetic properties, we compared t hese three enzymes for a better understanding of their structure-funct ion relationships. Three surface loops surrounding the active site (be ta 5 loop, beta 9 loop, lid domain) an believed to play an important r ole in substrate selectivity.