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Structure of human pancreatic lipase
F K Winkler1, A D'Arcy, W Hunziker
1Central Research Units, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Nature
|February 22, 1990
Summary
Human pancreatic lipase, crucial for fat digestion, has a determined 3D structure. Its catalytic Ser 152 residue is key for enzyme function, despite structural differences from serine proteases.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Pancreatic lipase is essential for dietary fat absorption, hydrolyzing triglycerides.
- Understanding its structure-function relationship is key to comprehending fat digestion.
Purpose of the Study:
- To determine the three-dimensional structure of human pancreatic lipase.
- To elucidate the catalytic mechanism and identify key residues involved in enzymatic activity.
Main Methods:
- X-ray crystallography was used to determine the enzyme's 3D structure.
- Complementary DNA sequencing established the primary amino acid sequence.
Main Results:
- The structure reveals Ser 152 as the essential nucleophilic residue for catalysis.
- This residue is part of an Asp-His-Ser triad, analogous to serine proteases but structurally distinct.
- The active site is protected by a surface loop, suggesting a role in interfacial activation.
Conclusions:
- The structural data confirm Ser 152's critical role in pancreatic lipase catalysis.
- Interfacial activation likely involves conformational changes of a surface loop.
- These findings have implications for understanding homologous lipases in other tissues.