Sandbox 51: Difference between revisions

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Pancreatic lipase 1hpl (EC 3.1.1.3) is a an enzyme involved with the digestion and absorption of triacylglycerols (fats) in the intestine. It is secreted by the pancreas into the duodenum where it participates in the initial stages of breaking down fats <ref>Voet, D.,etc. "Fundamentals of Biochemistry: Life at the Molecular Level" John Wiley and Sons, Inc: New Jersey, 2008.</ref>

==Structure==

1hpl is the horse pancreatic lipase enzyme that is thought to have a similar structure and function to the human pancreatic lipase. The <scene name='Sandbox_51/Lipase_crystal_structure/1'> Crystal Structure</scene> of the human pancreatic lipase has not yet been published. Lipase is a dimer of two <scene name='Sandbox_51/Lipase_crystal_structure/3'>monomers</scene> with 449 amino acid residues interacting with one <scene name='Sandbox_51/Ligand_position/2'>Calcium Ligand</scene> each. The calcium ion <scene name='Sandbox_51/Calcium_orientation/2'>orientation</scene> shows that the molecule is located between acidic residues Arg, Asp and Glu. The enzyme has 13 alpha helices (pink) and 22 beta sheets (yellow) per subunit, as displayed in the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene> <ref>Egloff, M.P., etc. "The 2.46 angstroms resolution structure of the pancreatic lipase colipase complex inhibited by a C11 alkyl phosphonate."(1995) J. Biochemistry 34: 2751-2762 [http://www.pdb.org/pdb/explore/explore.do?structureId=1lpb]</ref>. The molecule has a varying degree of <scene name='Sandbox_51/Polar_structure/3'>polar and hydrophobic residues</scene> interspersed within the molecules (polar are shown in purple and hydrophobic in white) <ref>Bourne, Y., etc. "Horse pancreatic lipase..."(1994) J.Mol.Biol. 238: 709-732 [http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL]</ref>. This is important because the enzyme actively digests at the lipid-water interface of the fatty micelles, requiring stability in both polar and non polar environments <ref>Fundamentals of Biochemistry...</ref>. Lipase is water soluble due ~~mostly~~ the the ~~alpha helices directly~~ hydrophobic sequences ~~inward to all polar residues~~ on the ~~surface~~. At enzyme activation and interaction with colipase, a confirmation change occurs to expose the more hydrophobic regions to the nonpolar lipid micelle. The enzyme has <scene name='Sandbox_51/Nc_terminal/1'>two domains</scene> of various composition specific for certain ~~interaction~~, an N-terminal (blue) and a C-terminal (red). In the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene>, the N-terminal domain has the hydrolase alpha/beta folding structure, consisting of an alpha-beta sheet consisting of 8 strands connected by helices. The C-terminal domain (enzyme colipase binds) has a beta-sheet ~~sandwhich~~ folding pattern <ref>Horse pancreatic lipase...</ref>. 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 Ser-His-Arg for the ester hydrolysis reaction (similar to that of a serine protease). The active site is covered by a 25-residue helical 'lid' blocking the binding site, unless appropriate conditions <ref>Fundamentals of Biochemistry...</ref>.

1hpl is the horse pancreatic lipase enzyme that is thought to have a similar structure and function to the human pancreatic lipase. The <scene name='Sandbox_51/Lipase_crystal_structure/1'> Crystal Structure</scene> of the human pancreatic lipase has not yet been published. Lipase is a dimer of two <scene name='Sandbox_51/Lipase_crystal_structure/3'>monomers</scene> with 449 amino acid residues interacting with one <scene name='Sandbox_51/Ligand_position/2'>Calcium Ligand</scene> each. The calcium ion <scene name='Sandbox_51/Calcium_orientation/2'>orientation</scene> shows that the molecule is located between acidic residues Arg, Asp and Glu. The enzyme has 13 alpha helices (pink) and 22 beta sheets (yellow) per subunit, as displayed in the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene> <ref>Egloff, M.P., etc. "The 2.46 angstroms resolution structure of the pancreatic lipase colipase complex inhibited by a C11 alkyl phosphonate."(1995) J. Biochemistry 34: 2751-2762 [http://www.pdb.org/pdb/explore/explore.do?structureId=1lpb]</ref>. The molecule has a varying degree of <scene name='Sandbox_51/Polar_structure/3'>polar and hydrophobic residues</scene> interspersed within the molecules (polar are shown in purple and hydrophobic in white) <ref>Bourne, Y., etc. "Horse pancreatic lipase..."(1994) J.Mol.Biol. 238: 709-732 [http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL]</ref>. This is important because the enzyme actively digests at the lipid-water interface of the fatty micelles, requiring stability in both polar and non polar environments <ref>Fundamentals of Biochemistry...</ref>. The enzyme also has six

<scene name='Sandbox_51/Disulfide_bons/1'>disulfide bonds</scene> per monomer. Lipase is water soluble due to the polar residues on the surface, and hydrophobic sequences on the interior. At enzyme activation and interaction with colipase, a confirmation change occurs to expose the more hydrophobic regions to the nonpolar lipid micelle.

==Active Site==

The enzyme has <scene name='Sandbox_51/Nc_terminal/1'>two domains</scene> of various composition specific for certain interactions, an N-terminal (blue) and a C-terminal (red). In the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene>, the N-terminal domain has the hydrolase alpha/beta folding structure, consisting of an alpha-beta sheet consisting of 8 strands connected by helices. The C-terminal domain (enzyme colipase binds) has a beta-sheet sandwich folding pattern <ref>Horse pancreatic lipase...</ref>. 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 Ser-His-Arg for the ester hydrolysis reaction (similar to that of a serine protease). The active site is covered by a 25-residue helical 'lid' blocking the binding site, unless appropriate conditions <ref>Fundamentals of Biochemistry...</ref>.

==Function==

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 Pancreatic lipase 1hpl (EC 3.1.1.3)  is a an enzyme involved with the digestion and absorption of triacylglycerols (fats) in the intestine.  It is secreted by the pancreas into the duodenum where it participates in the initial stages of breaking down fats <ref>Voet, D.,etc. "Fundamentals of Biochemistry: Life at the Molecular Level" John Wiley and Sons, Inc: New Jersey, 2008.</ref>
 ==Structure==
-hpl is the horse pancreatic lipase enzyme that is thought to have a similar structure and function to the human pancreatic lipase.  The  <scene name='Sandbox_51/Lipase_crystal_structure/1'> Crystal Structure</scene> of the human pancreatic lipase has not yet been published.   Lipase is a dimer of two <scene name='Sandbox_51/Lipase_crystal_structure/3'>monomers</scene> with 449 amino acid residues interacting with one <scene name='Sandbox_51/Ligand_position/2'>Calcium Ligand</scene> each.  The calcium ion <scene name='Sandbox_51/Calcium_orientation/2'>orientation</scene> shows that the molecule is located between acidic residues Arg, Asp and Glu.  The enzyme has 13 alpha helices (pink) and 22 beta sheets (yellow) per subunit, as displayed in the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene> <ref>Egloff, M.P., etc. "The 2.46 angstroms resolution structure of the pancreatic lipase colipase complex inhibited by a C11 alkyl phosphonate."(1995) J. Biochemistry 34: 2751-2762 [http://www.pdb.org/pdb/explore/explore.do?structureId=1lpb]</ref>.  The molecule has a varying degree of <scene name='Sandbox_51/Polar_structure/3'>polar and hydrophobic residues</scene> interspersed within the molecules (polar are shown in purple and hydrophobic in white) <ref>Bourne, Y., etc. "Horse pancreatic lipase..."(1994) J.Mol.Biol. 238: 709-732 [http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL]</ref>.  This is important because the enzyme actively digests at the lipid-water interface of the fatty micelles, requiring stability in both polar and non polar environments <ref>Fundamentals of Biochemistry...</ref>. Lipase is water soluble due mostly the the alpha helices directly hydrophobic sequences inward to all polar residues on the surface.  At enzyme activation and interaction with colipase, a confirmation change occurs to expose the more hydrophobic regions to the nonpolar lipid micelle.  The enzyme has <scene name='Sandbox_51/Nc_terminal/1'>two domains</scene> of various composition specific for certain interaction, an N-terminal (blue) and a C-terminal (red).  In the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene>, the N-terminal domain has the hydrolase alpha/beta folding structure, consisting of an alpha-beta sheet consisting of 8 strands connected by helices. The C-terminal domain (enzyme colipase binds) has a beta-sheet sandwhich folding pattern <ref>Horse pancreatic lipase...</ref>. 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 Ser-His-Arg for the ester hydrolysis reaction (similar to that of a serine protease).  The active site is covered by a 25-residue helical 'lid' blocking the binding site, unless appropriate conditions <ref>Fundamentals of Biochemistry...</ref>.
+hpl is the horse pancreatic lipase enzyme that is thought to have a similar structure and function to the human pancreatic lipase.  The  <scene name='Sandbox_51/Lipase_crystal_structure/1'> Crystal Structure</scene> of the human pancreatic lipase has not yet been published.   Lipase is a dimer of two <scene name='Sandbox_51/Lipase_crystal_structure/3'>monomers</scene> with 449 amino acid residues interacting with one <scene name='Sandbox_51/Ligand_position/2'>Calcium Ligand</scene> each.  The calcium ion <scene name='Sandbox_51/Calcium_orientation/2'>orientation</scene> shows that the molecule is located between acidic residues Arg, Asp and Glu.  The enzyme has 13 alpha helices (pink) and 22 beta sheets (yellow) per subunit, as displayed in the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene> <ref>Egloff, M.P., etc. "The 2.46 angstroms resolution structure of the pancreatic lipase colipase complex inhibited by a C11 alkyl phosphonate."(1995) J. Biochemistry 34: 2751-2762 [http://www.pdb.org/pdb/explore/explore.do?structureId=1lpb]</ref>.  The molecule has a varying degree of <scene name='Sandbox_51/Polar_structure/3'>polar and hydrophobic residues</scene> interspersed within the molecules (polar are shown in purple and hydrophobic in white) <ref>Bourne, Y., etc. "Horse pancreatic lipase..."(1994) J.Mol.Biol. 238: 709-732 [http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL]</ref>.  This is important because the enzyme actively digests at the lipid-water interface of the fatty micelles, requiring stability in both polar and non polar environments <ref>Fundamentals of Biochemistry...</ref>. The enzyme also has six
+<scene name='Sandbox_51/Disulfide_bons/1'>disulfide bonds</scene> per monomer.  Lipase is water soluble due to the polar residues on the surface, and hydrophobic sequences on the interior.  At enzyme activation and interaction with colipase, a confirmation change occurs to expose the more hydrophobic regions to the nonpolar lipid micelle.
+==Active Site==
+The enzyme has <scene name='Sandbox_51/Nc_terminal/1'>two domains</scene> of various composition specific for certain interactions, an N-terminal (blue) and a C-terminal (red).  In the <scene name='Sandbox_51/Secondary_structure/2'>secondary structure</scene>, the N-terminal domain has the hydrolase alpha/beta folding structure, consisting of an alpha-beta sheet consisting of 8 strands connected by helices. The C-terminal domain (enzyme colipase binds) has a beta-sheet sandwich folding pattern <ref>Horse pancreatic lipase...</ref>. 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 Ser-His-Arg for the ester hydrolysis reaction (similar to that of a serine protease).  The active site is covered by a 25-residue helical 'lid' blocking the binding site, unless appropriate conditions <ref>Fundamentals of Biochemistry...</ref>.
 ==Function==