Lipase: Difference between revisions

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Pancreatic lipase is a 50 kDa protein. While the crystallographic [[asymmetric unit]] contains two identical chains, information (REMARK 350) in the data file [[1hpl]] indicates that the dimer is a crystallization artifact, and that the functional form (also called the [[biological assembly]]) is a single chain (monomer). The chain consists of 449 residues <ref name= "1HPL PDB">[http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL] 1HPL PDB</ref>. The <scene name='Lipase/Secondary_structures/1'>secondary structure</scene>s of lipase (in one subunit) include 102 residues which create 13 alpha helices, shown in red, and 139 residues involved in beta sheets totaling 28 strands, shown in gold. The alpha helices account for 22% of the protein, while the beta sheets comprise 30%. Each chain contains two well defined <scene name='Lipase/N_and_c_terminus/1'>domains</scene>. The N terminal domain, shown in blue, is characterized by an alpha/beta hydrolase fold. While the C terminal domain, shown in green, contains a beta sheet sandwich which interacts with colipase <ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL</ref>. Each monomer and dimer structure of lipase are held together by disulfide bonds, hydrogen bonds, and electrostatic interactions (salt bridges). Lipase has 12 total <scene name='Lipase/Disulfide_bonds/2'>disulfide bonds</scene> between cysteine residues. <scene name='Lipase/Salt_bridges/1'>Salt bridges</scene> are formed between the positively charge nitrogens (blue) in Arg and Lys, and negative oxygens (red) in Asp and Glu residues. <scene name='Lipase/Hydrogen_bonds/2'>Hydrogen bonds</scene> (in yellow) also stabilize the enzyme between main chain and side chain atoms. Lipase has a distinct distribution of <scene name='Lipase/Hphobic_residues/3'>hydrophobic and hydrophilic</scene> residues (purple spacefill represents polar residues). Hydrophobic collapse contributes to much of the secondary and tertiary structures, as the <scene name='Lipase/Surface/1'>hydrophobic core residues</scene> (shown in white) make up the interior of the protein, while polar residues (transparent blue) are on the surface <ref>http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=1HPL</ref>. In addition, lipase has two <scene name='Lipase/Lipase_ligand/1'>calcium ligands</scene>. One is buried in each monomer subunit. The calcium ion is essential to protein folding and enzyme activity <ref>http://www.springerlink.com/content/g5h1613440115701/fulltext.pdf</ref>. The image shows the green calcium ion in subunit A, coordinated by Glu187, Arg190, Asp192, and Asp195 residues. The Ca(+2) charge is stabilized by negatively charged glutamate and aspartate residues, and the oxygen atoms from two water molecules (pink).

In addition, lipase has a unique <scene name='Lipase/Lid/2'>lid</scene> (green) that blocks solvent from entering the active site (red). The lid is a 25-residue helical structure that protects the oxyanion hole. The lid (yellow) is especially important to substrate binding as it undergoes a dramatic shift that alters the secondary structure of the lipase binding site from a <scene name='Lipase/Closed_lid/1'>closed lid structure</scene> (active site in red) to an <scene name='Lipase/Open_ring/1'>open ring structure</scene> (active site in blue, triacylglyceride in spacefill) <ref>Fundamentals of Biochemistry...</ref>. 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>.

In addition, lipase has a unique <scene name='Lipase/Lid/2'>lid</scene> (green) that blocks solvent from entering the active site (red). The lid is a 25-residue helical structure that protects the oxyanion hole. The lid (yellow) is especially important to substrate binding as it undergoes a dramatic shift that alters the secondary structure of the lipase binding site from a <scene name='Lipase/Closed_lid/1'>closed lid structure</scene> (active site in red) to an <scene name='Lipase/Open_ring/1'>open ring structure</scene> (active site in blue, triacylglyceride in spacefill) <ref>Fundamentals of Biochemistry...</ref> (see [[Lipase lid morph]] for an animation of this transition). 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>.

== '''Colipase Coenzyme''' ==

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 Pancreatic lipase is a 50 kDa protein. While the crystallographic [[asymmetric unit]] contains two identical chains, information (REMARK 350) in the data file [[1hpl]] indicates that the dimer is a crystallization artifact, and that the functional form (also called the [[biological assembly]]) is a single chain (monomer). The chain consists of 449 residues <ref name= "1HPL PDB">[http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL] 1HPL PDB</ref>. The <scene name='Lipase/Secondary_structures/1'>secondary structure</scene>s of lipase (in one subunit) include 102 residues which create 13 alpha helices, shown in red, and 139 residues involved in beta sheets totaling 28 strands, shown in gold. The alpha helices account for 22% of the protein, while the beta sheets comprise 30%.  Each chain contains two well defined <scene name='Lipase/N_and_c_terminus/1'>domains</scene>. The N terminal domain, shown in blue, is characterized by an alpha/beta hydrolase fold.  While the C terminal domain, shown in green,  contains a beta sheet sandwich which interacts with colipase <ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL</ref>.  Each monomer and dimer structure of lipase are held together by disulfide bonds, hydrogen bonds, and electrostatic interactions (salt bridges).  Lipase has 12 total <scene name='Lipase/Disulfide_bonds/2'>disulfide bonds</scene> between cysteine residues.  <scene name='Lipase/Salt_bridges/1'>Salt bridges</scene> are formed between the positively charge nitrogens (blue) in Arg and Lys, and negative oxygens (red) in Asp and Glu residues.  <scene name='Lipase/Hydrogen_bonds/2'>Hydrogen bonds</scene> (in yellow) also stabilize the enzyme between main chain and side chain atoms.  Lipase has a distinct distribution of <scene name='Lipase/Hphobic_residues/3'>hydrophobic and hydrophilic</scene> residues (purple spacefill represents polar residues).  Hydrophobic collapse contributes to much of the secondary and tertiary structures, as the <scene name='Lipase/Surface/1'>hydrophobic core residues</scene> (shown in white) make up the interior of the protein, while polar residues (transparent blue) are on the surface <ref>http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=1HPL</ref>.  In addition, lipase has two <scene name='Lipase/Lipase_ligand/1'>calcium ligands</scene>. One is buried in each monomer subunit. The calcium ion is essential to protein folding and enzyme activity <ref>http://www.springerlink.com/content/g5h1613440115701/fulltext.pdf</ref>.  The image shows the green calcium ion in subunit A, coordinated by Glu187, Arg190, Asp192, and Asp195 residues.  The Ca(+2) charge is stabilized by negatively charged glutamate and aspartate residues, and the oxygen atoms from two water molecules (pink).
-In addition, lipase has a unique <scene name='Lipase/Lid/2'>lid</scene> (green) that blocks solvent from entering the active site (red).   The lid is a 25-residue helical structure that protects the oxyanion hole.  The lid (yellow) is especially important to substrate binding as it undergoes a dramatic shift that alters the secondary structure of the lipase binding site from a <scene name='Lipase/Closed_lid/1'>closed lid structure</scene> (active site in red) to an <scene name='Lipase/Open_ring/1'>open ring structure</scene> (active site in blue, triacylglyceride in spacefill) <ref>Fundamentals of Biochemistry...</ref>. 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>.
+In addition, lipase has a unique <scene name='Lipase/Lid/2'>lid</scene> (green) that blocks solvent from entering the active site (red).   The lid is a 25-residue helical structure that protects the oxyanion hole.  The lid (yellow) is especially important to substrate binding as it undergoes a dramatic shift that alters the secondary structure of the lipase binding site from a <scene name='Lipase/Closed_lid/1'>closed lid structure</scene> (active site in red) to an <scene name='Lipase/Open_ring/1'>open ring structure</scene> (active site in blue, triacylglyceride in spacefill) <ref>Fundamentals of Biochemistry...</ref> (see [[Lipase lid morph]] for an animation of this transition). 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>.
 == '''Colipase Coenzyme''' ==