Sandbox 51: Difference between revisions

In addition to the effects of bile salts, Lipase is activated by the coenzyme colipase, which binds to the C-terminal non-catalytic domain.  Upon binding, active lipase is stabilized for the hydrophobic interaction with the triacylglycerides <ref>Fundamentals of Biochemistry...</ref>.  Colipase must be present for activation of lipase.  Lipase activation at the lipid-water interface of triacylglycerides, in the presence of colipase and bile salts, is known as interfacial activation. Colipase is also secreted in the pancreas, but in its inactive form, which must be activated by trypsin before interacting with lipase <ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref>.  Colipase and lipase <scene name='Sandbox_51/Contacts/3'>contacts</scene> are at opposite of the active site on the C-terminal, including polar interactions such as <scene name='Sandbox_51/Salt_bridges/2'>salt bridges</scene> and van der waals forces which stabilize the interaction <ref>van Tilbeurgh H, etc."Structure of the pancreatic lipase-procolipase complex",  1992 Sep 10;359(6391):159-62. PMID:1522902.[http://www.proteopedia.org/wiki/index.php/1n8s]</ref>. <scene name='Sandbox_51/Lipase_and_colipase/1'>Colipase and lipase in complex with a triacylglyceride</scene> shows a unique feature of lipase is the lid over the active sight.  Once colipase has anchored lipase to the lipid-water membrane, a surface change occurs.  The lid of lipase has been acknowledged as essential to lipase action.  The 10 residue beta-5 loop changes confirmation exposing lipase's oxyanion hole and hydrophobic surface.  Before colipase binding, lipase is in the <scene name='Sandbox_51/Closed_lid/2'>closed confirmation</scene> where the beta-5 loop(residues 76-84, in pink) and lid (residues 237-261, yellow) serves to protect the oxyanion hole from solvent interaction.  The <scene name='Sandbox_51/Mutated_open_ring/4'>open lid</scene> structure is accompanied by peptide shifts- one such important shift is at residues 240-252 (part of the lid residues in yellow, close in vicinity to the active site).  The peptide shifts accompany the lid opening, and increase hydrophobic surface exposure initiating the reaction with the lipid.  Colipase hydrophobic loops interact with the hydrophobic atmosphere of the triacylglyceride initiating lipase active site binding to the lipid. Once colipase is bound, lipase initiates a serine-like hydrolysis involving His, Asp, Ser residues in the catalytic triad releasing the lipid products <ref>Fundamentals of Biochemistry...</ref>. In the reaction, serine attacks the ester, forming an acyl-enzyme intermediate.  The His and Asp residues help to stabilize the oxyanion intermediate through hydrogen bonding.  Water enters the active site and reacts to release lipase and free the fatty acid. This acylation and deacylation reaction is usually completely reversible.