Interfacial activation of the lipase-procolipase complex by mixed micelles revealed by X-ray crystallography

• Published in: Nature (London) Vol. 362; no. 6423; pp. 814 - 820
• Main Authors: van Tilbeurgh, Herman, Egloff, Marie-Pierre, Martinez, Chrislaine, Rugani, Nathalie, Verger, Robert, Cambillau, Christian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 29.04.1993; Nature Publishing Group
• Subjects: Analytical, structural and metabolic biochemistry; Binding Sites; Biological and medical sciences; Colipases - chemistry; Computer Simulation; Crystallography; Enzyme Precursors; Enzymes; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrolases; Lipase - chemistry; Macromolecular Substances; Micelles; Models, Molecular; Oils & fats; Pancreas - enzymology; Phosphatidylcholines - chemistry; Protein Conformation; Protein Precursors - chemistry; Taurodeoxycholic Acid - chemistry; X-Ray Diffraction; X-rays; Enzyme; Active site; Triacylglycerol lipase; Molecular complex; Spatial structure; Induced conformation; Crystalline structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/362814a0

The three-dimensional structure of the lipase-procolipase complex, co-crystallized with mixed micelles of phosphatidylcholine and bile salt, has been determined at 3 A resolution by X-ray crystallography. The lid, a surface helix covering the catalytic triad of lipase, adopts a totally different conformation which allows phospholipid to bind to the enzyme's active site. The open lid is an essential component of the active site and interacts with procolipase. Together they form the lipid-water interface binding site. This reorganization of the lid structure provokes a second drastic conformational change in an active site loop, which in its turn creates the oxyanion hole (induced fit).