Sandbox 51: Difference between revisions

The <scene name='Sandbox_51/Active_site/3'>active site</scene> of the lipase molecule is found in the N-terminal domain (residues 1-336) and contains a <scene name='Sandbox_51/Catalytic_tria/1'>catalytic triad</scene> consisting of a Ser152-His263-Arg176 for the ester hydrolysis reaction (similar to that of a serine protease).  The catalytic triad and regions around it are thought to be the best conserved aspects of lipase throughout the lipase family.  The active site is covered by a 25-residue helical 'lid' blocking the binding site <ref>Fundamentals of Biochemistry... <scene name='Sandbox_51/Lipase_and_colipase/2'>Lipase and colipase</scene> in complex with a triacylglyceride shows the unique lid (yellow) and beta-5 loop (pink) essential to catalysis.  The 10 residue beta-5 loop changes confirmation when colipase binds, exposing lipase's oxyanion hole and hydrophobic surface.  Before colipase binding however, lipase is in the <scene name='Sandbox_51/Closed_lid/4'>closed lid</scene> structure where the beta-5 loop (residues 76-84, in pink) and lid (residues 237-261, yellow) protect the oxyanion hole from solvent interaction.  The <scene name='Sandbox_51/Mutated_open_ring/6'>open ring</scene> structure is accompanied by peptide shift which increase the hydrophobic surface area initiating the reaction with the lipid.  one such important shift is at residues 240-253 (in yellow), in the lid structure, very close to the active site.  Also, it is evident from the image that part of the beta-5 loop interacts with colipase in the open state. The lid opening is accompanied by a change in secondary structure from a mostly beta-extended confirmation to a structure where more than half the active site is formed from alpha helices <ref> Thomas, A. etc. "Role of the Lid Hydrophobicity Pattern in Pancreatic Lipase Activity", The Journal of Biological Chemistry, 2005 September 22; 270 (48): 40074-40083. </ref>.