title: Gastric lipase: crystal structure and activity.
abstract: Fat digestion in humans requires not only the classical pancreatic lipase but also gastric lipase, which is stable and active despite the highly acidic stomach environment. We have solved the structure of recombinant human gastric lipase at 3.0 A resolution, the first structure to be described within the mammalian acid lipase family. This globular enzyme (379 residues) consists of a core domain, belonging to the alpha/beta hydrolase fold family, and an extrusion domain. It possesses a classical catalytic triad (Ser 153, His 353, Asp 324) and an oxyanion hole (NH groups of Gln 154 and Leu 67). Four N-glycosylation sites were identified on the electron density maps. The catalytic serine is deeply buried under the extrusion domain, which is composed of a 'cap' domain and a segment consisting of 30 residues, which can be defined as a lid. Its displacement is necessary for the substrates to access the active site. A phosphonate inhibitor was positioned in the active site which clearly suggests the location of the hydrophobic substrate binding site.
authors.affiliation: Laboratoire de Lipolyse Enzymatique, CNRS-IFR1 UPR 9025, 31 chemin Joseph Aiguier, 13402, Marseilles, France.
authors.forename: S
authors.initials: S
authors.lastname: Canaan
authors.forename: A
authors.initials: A
authors.lastname: Roussel
authors.forename: R
authors.initials: R
authors.lastname: Verger
authors.forename: C
authors.initials: C
authors.lastname: Cambillau
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013270:Stomach / Q000201:enzymology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D014280:Triglycerides; D008049:Lipase