PANCREATIC LIPASE-RELATED PROTEIN TYPE-I - A SPECIALIZED LIPASE OR ANINACTIVE ENZYME

The existence of pancreatic lipase-related protein 1 (PLRP1) in verteb rates has been postulated based on the screening of pancreatic cDNA li braries from different species. In this paper, we report the presence of variable amounts of PLRP1 relative to colipase-dependent lipase (PL ) in adults from several species. Only a very low lipase activity coul d be detected for native or recombinant PLRP1 using a large variety of substrates and conditions. Interestingly, this activity is dependent on the presence of bile salts and colipase and PLRP1 is shown to posse ss the same affinity as PL for colipase. Modelling investigations reve aled some interesting differences between PLRP1 and FL, notably concer ning substitutions in the C-terminal domain which might affect the ben ding motion of this domain relative to the N-terminal domain in PLRP1, The potential impact of these differences on the lack of lipase activ ity of PLRP1 was investigated using chimeric proteins designed by C-te rminal domain exchange between dog PLRP1 and horse FL. Analysis of the catalytic properties of the chimera clearly indicated that the C-term inal domain exchange neither inactivates the horse enzyme nor results in an active dog PLRP1, From these findings, it can be concluded that the PLRP1 C-terminal domain is fully functional with respect to colipa se binding. The lack of lipase activity or the still undetermined func tion of PLRP1 is likely to result mainly from particular features of t he N-terminal domain.