Title : Crystal structure of human
gastric lipase and model of
lysosomal acid lipase , two lipolytic
enzymes of medical interest
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 report here 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 a "cap" domain , which is analogous to that present in serine carboxypeptidases
- 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 a segment consisting of 30 residues, which can be defined as a lid and belonging to the cap domain
- The displacement of the lid is necessary for the substrates to have access to Ser-153
- A phosphonate inhibitor was position ed in the active site that clearly suggests the location of the hydrophobic substrate binding site
- The lysosomal acid lipase was modeled by homology, and possible explanations for some previously reported mutations leading to the cholesterol ester storage disease are given based on the present model