Accueil > Publications > Recherche par années > Années 1990 > 1998

Bezzine, S ; Roussel, A ; de Caro, J ; Gastinel, L ; de Caro, A ; Carriere, F ; Leydier, S ; Verger, R ; Cambillau, C

An inactive pancreatic lipase-related protein is activated into a triglyceride-lipase by mutagenesis based on the 3-D structure

Chemistry and Physics of Lipids 93 (1-2) 103-114

par Administrateur - publié le

Abstract :

Both classical dog pancreatic lipase (DPL) and dog pancreatic lipase-related protein 1 (DPLRP1) have been found to be secreted by the exocrine pancreas. These two proteins were purified to homogeneity from canine pancreatic juice and no significant catalytic activity was observed with DPLRP1 on any of the substrates tested : di-and tri-glycerides ; phospholipids (PC) ; etc. DPLRP1 was crystallized and its structure solved by molecular replacement and refined at a resolution of 2.10 Angstrom. Its structure is similar to that of the classical pancreatic lipase (PL) structures determined in the absence of any inhibitors or micelles. The lid domain that controls the access to the active site was found to have a closed conformation. An amino-acid substitution (Ala 178 Val) in the DPLRP1 was suspected of being responsible for the absence of enzymatic activity by inducing a steric clash with one of the acyl chain observed in the structures of chiral C11 alkyl phosphonate inhibitors, bound to the classical FL.