Sandbox 50: Difference between revisions
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== Colipase Binding == | == Colipase Binding == | ||
When bile salts accumulate at the lid/water interface, adsoprtion of the enzyme on its substrates is prohibited. In order to overcome this inhibitory effect, colipase binds to HPL and anchors lipase at the interface coated with bile salts.<ref>http://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1992.tb16926.x/pdf</ref> | When bile salts accumulate at the lid/water interface, adsoprtion of the enzyme on its substrates is prohibited. In order to overcome this inhibitory effect, colipase binds to HPL and anchors lipase at the interface coated with bile salts.<ref>http://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1992.tb16926.x/pdf</ref> | ||
When bound to colipase,HPL exists in its active, <scene name='Sandbox_50/Colipase_binding/1'>open configuration</scene>.<ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1ETH</ref> Here chains A and C (blue and pink) are the chians from the original HPL protein, and chains B and D (green and yellow) are colipase peptides. | When bound to colipase,HPL exists in its active, <scene name='Sandbox_50/Colipase_binding/1'>open configuration</scene> (porcine lipase/colipase model shown here).<ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1ETH</ref> Here chains A and C (blue and pink) are the chians from the original HPL protein, and chains B and D (green and yellow) are colipase peptides. | ||
Rate studies show that the disassociation constant of the lipase-colipase complex is 101.1x10^−9 M. When the substrate is absent, the disassociation constant increases by several orders, indicating that disassociation of colipase from lipase increases when no substrates are present. These studies confirm that pancreatic lipase has many highly <scene name='Sandbox_50/Conserved_residues/1'>conserved residues</scene>, as horse, ox, pig, rat, dog, and chicken colipases all can activate HPL and have similar disassociation constants. <ref>http://www.sciencedirect.com/science/article/pii/S0300908481801964</ref> | Rate studies show that the disassociation constant of the lipase-colipase complex is 101.1x10^−9 M. When the substrate is absent, the disassociation constant increases by several orders, indicating that disassociation of colipase from lipase increases when no substrates are present. These studies confirm that pancreatic lipase has many highly <scene name='Sandbox_50/Conserved_residues/1'>conserved residues</scene>, as horse, ox, pig, rat, dog, and chicken colipases all can activate HPL and have similar disassociation constants. <ref>http://www.sciencedirect.com/science/article/pii/S0300908481801964</ref> | ||
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In the presence of colipase, the enzyme is activated which moves the <scene name='Sandbox_50/N-terminal_flap/1'>N-terminal flap</scene> (shown in red) which is composed of amino acids 216-239. The N-terminal flap moves in a concerted fashion along with the C-terminal domain to reveal the active site (green), allowing it to bind with a substrate. It is hypothesized that this flexibility may have significance in binding the colipase-lipase complex with the water-lipid interface.<ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1ETH</ref> The reorganization of the flap also induces a second conformational change that creates the oxyanion hole.<ref>http://www.nature.com/nature/journal/v362/n6423/abs/362814a0.html</ref> | In the presence of colipase, the enzyme is activated which moves the <scene name='Sandbox_50/N-terminal_flap/1'>N-terminal flap</scene> (shown in red) which is composed of amino acids 216-239. The N-terminal flap moves in a concerted fashion along with the C-terminal domain to reveal the active site (green), allowing it to bind with a substrate. It is hypothesized that this flexibility may have significance in binding the colipase-lipase complex with the water-lipid interface.<ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1ETH</ref> The reorganization of the flap also induces a second conformational change that creates the oxyanion hole.<ref>http://www.nature.com/nature/journal/v362/n6423/abs/362814a0.html</ref> | ||
<scene name='Sandbox_50/Put_water_bond/1'>put water</scene> | |||
<scene name='Sandbox_50/H_bonds/1'>h bonds</scene> | |||
== Active Site and Mechanism == | == Active Site and Mechanism == | ||