title: Pancreatic lipase-related protein type 1: a double mutation restores a significant lipase activity.
abstract: Besides the active pancreatic lipase (PL) which plays a major role in dietary fat digestion, the presence of a pancreatic lipase related protein 1 (PLRP1) displaying a very low lipolytic activity has been reported in vertebrates. It has been suggested that the reduced lipolytic activity of PLRP1 results from specific features of the N-terminal domain of the protein. Therefore, based on sequence comparison between PL and PLRP1 and modelling experiments, several residues located in the vicinity of the active site pocket of both enzymes have been mutated. In this paper, we report that, as regards to PL, two substitutions in positions 179 and 181 in PLRP1 account for the very low lipolytic activity of the protein. Indeed, substituting these residues (V179 and A181) in PLRP1 for those found in PL (A179 and P181), restores a significant lipolytic activity for PLRP1.
authors.affiliation: Unité de Bioénergétique et Ingénierie des Protéines, UPR 9036 CNRS, Marseille, France. crenon@ibsm.cnrs-mrs.fr
authors.forename: I
authors.initials: I
authors.lastname: Crenon
authors.forename: S
authors.initials: S
authors.lastname: Jayne
authors.forename: B
authors.initials: B
authors.lastname: Kerfelec
authors.forename: J
authors.initials: J
authors.lastname: Hermoso
authors.forename: D
authors.initials: D
authors.lastname: Pignol
authors.forename: C
authors.initials: C
authors.lastname: Chapus
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D006736:Horses; D066298:In Vitro Techniques; D007700:Kinetics; D008049:Lipase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008066:Lipolysis / Q000235:genetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010179:Pancreas / Q000201:enzymology*; D017354:Point Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D008049:Lipase; C075987:pancreatic lipase-related protein 1