Gastric lipase: crystal structure and activity

Fat digestion in humans requires not only the classical pancreatic lipase b ut also gastric lipase, which is stable and active despite the highly acidi c stomach environment. We have solved the structure of recombinant human ga stric lipase at 3.0 Angstrom resolution, the first structure to be describe d within the mammalian acid lipase family. This globular enzyme (379 residu es) consists of a core domain, belonging to the alpha/beta hydrolase fold f amily, and an extrusion domain. It possesses a classical catalytic triad (S er 153, His 353, Asp 324) and an oxyanion hole (NH groups of Gln 154 and Le u 67). Four N-glycosylation sites were identified on the electron density m aps. The catalytic serine is deeply buried under the extrusion domain, whic h is composed of a 'cap' domain and a segment consisting of 30 residues, wh ich can be defined as a lid. Its displacement is necessary for the substrat es to access the active site. A phosphonate inhibitor was positioned in the active site which clearly suggests the location of the hydrophobic substra te binding site. (C) 1999 Elsevier Science B.V. All rights reserved.