STRUCTURE-FUNCTION-RELATIONSHIPS IN NATURALLY-OCCURRING MUTANTS OF PANCREATIC LIPASE

From primary structure comparison, the pancreatic lipase family is now divided into three subgroups: classical pancreatic lipases, pancreati c lipase-related proteins 1 (RPI) and pancreatic lipase-related protei ns 2 (RP2). Among the RP2 subfamily, the guinea-pig and coypu enzymes share kinetic properties which differ from those of classical pancreat ic lipases. Both enzymes display a high phospholipase activity and are not interfacially activated using a short chain triglyceride as subst rate. Their activity towards insoluble triglycerides is inhibited by m icellar concentrations of bile salts and is not restored by addition o f colipase. These atypical kinetic properties are discussed in the lig ht of amino acid sequence comparison between RP2 and classical pancrea tic lipases, based on the closed and open conformations of the 3-D str ucture of human pancreatic lipase.