Sandbox 44
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The <scene name='Sandbox_44/Structure_of_lipase/1'>structure of lipase</scene> displays the enzyme in its natural form, with its two identical chains, each consisting of 449 amino acid residues. The <scene name='Sandbox_44/Secondary_structure/3'>secondary structures</scene> of human pancreatic lipase consists of 30% beta sheets (shown in orange), and 22% alpha helices (shown in fuschia). Here, beta sheets are depicted as planks, and alpha helices are shown as rockets. The remaining 48% of the enzyme's secondary structure consists of ordered, nonrepetitive sequence structure (shown in white) in contrast to the alpha helices and beta sheets. This even distribution of 48% ordered nonrepetitive structure to 52% alpha helix/beta sheet structure correlates to the appearance of the structure of lipase, which appears even to the casual observer to be about half alpha helix/beta sheet structure, and half ordered nonrepetitive structure depicted through the looping connective lines. This secondary structure of the enzyme, however, is formed due to the nature of the hydrogen bonding in between the main chains of lipase. These <scene name='Sandbox_44/Hydrogen_bonding/1'>hydrogen bonds</scene> can be seen throughout the structure of lipase, displayed here in bright yellow for clarity. <p> | The <scene name='Sandbox_44/Structure_of_lipase/1'>structure of lipase</scene> displays the enzyme in its natural form, with its two identical chains, each consisting of 449 amino acid residues. The <scene name='Sandbox_44/Secondary_structure/3'>secondary structures</scene> of human pancreatic lipase consists of 30% beta sheets (shown in orange), and 22% alpha helices (shown in fuschia). Here, beta sheets are depicted as planks, and alpha helices are shown as rockets. The remaining 48% of the enzyme's secondary structure consists of ordered, nonrepetitive sequence structure (shown in white) in contrast to the alpha helices and beta sheets. This even distribution of 48% ordered nonrepetitive structure to 52% alpha helix/beta sheet structure correlates to the appearance of the structure of lipase, which appears even to the casual observer to be about half alpha helix/beta sheet structure, and half ordered nonrepetitive structure depicted through the looping connective lines. This secondary structure of the enzyme, however, is formed due to the nature of the hydrogen bonding in between the main chains of lipase. These <scene name='Sandbox_44/Hydrogen_bonding/1'>hydrogen bonds</scene> can be seen throughout the structure of lipase, displayed here in bright yellow for clarity. <p> | ||
There are two main chains in human pancreatic lipase, shown here as Chain A and Chain B. <scene name='Sandbox_44/Chain_a/1'>Chain A</scene> (in blue) is exactly identical to <scene name='Sandbox_44/Chain_b/1'>Chain B</scene> (in green), and each chain has two domains which can be identified through <scene name='Sandbox_44/N-c_rainbow/1'>N terminus to C terminus labeling</scene>. This rainbow labeling displays the N-terminus domain of each chain in blue, leading in a color spectrum fashion to the C-terminus domain of each chain in red. These two sections of each chain are not identical in composition, however, as the N-terminus 337 residues long, comprised mainly in a 3 layer sandwich known as alpha, beta, alpha sandwich. The C-terminus, in comparison, contains a mere 112 residues that are ordered primarily in beta sandwich fashion. The C-terminus of lipase is where its enzyme colipase binds.</p> | There are two main chains in human pancreatic lipase, shown here as Chain A and Chain B. <scene name='Sandbox_44/Chain_a/1'>Chain A</scene> (in blue) is exactly identical to <scene name='Sandbox_44/Chain_b/1'>Chain B</scene> (in green), and each chain has two domains which can be identified through <scene name='Sandbox_44/N-c_rainbow/1'>N terminus to C terminus labeling</scene>. This rainbow labeling displays the N-terminus domain of each chain in blue, leading in a color spectrum fashion to the C-terminus domain of each chain in red. These two sections of each chain are not identical in composition, however, as the N-terminus 337 residues long, comprised mainly in a 3 layer sandwich known as alpha, beta, alpha sandwich. The C-terminus, in comparison, contains a mere 112 residues that are ordered primarily in beta sandwich fashion. The C-terminus of lipase is where its enzyme colipase binds.</p> | ||
| - | <p>The <scene name='Sandbox_44/Active_site_chain_a/1'>active site of Chain A</scene> is seen here highlighted in yellow, located within the N-terminus in residues 1-336. This active site contains a catalytic triad of Ser 152, His 263, and Asp 176 that facilitate the ester hydrolysis reaction carried out by lipase. The identical <scene name='Sandbox_44/Active_site_2/1'>active site of Chain B</scene> is shown here in red, also facilitating the reaction, the mechanism of which will be discussed below. | + | <p>The <scene name='Sandbox_44/Active_site_chain_a/1'>active site of Chain A</scene> is seen here highlighted in yellow, located within the N-terminus in residues 1-336. This active site contains a catalytic triad of Ser 152, His 263, and Asp 176 that facilitate the ester hydrolysis reaction carried out by lipase. This catalytic triad is very similar to that in a serine protease enzyme. However, if no lipid micelles are present for digestion, the active site of lipase (containing this catalytic triad of Ser, His, and Asp) is covered with a "lid" composed of 25 residues in a helical fashion.</p> |
| + | <p>The identical <scene name='Sandbox_44/Active_site_2/1'>active site of Chain B</scene> is shown here in red, also facilitating the reaction, the mechanism of which will be discussed below. | ||
</p> | </p> | ||
<p> Each of the two chains of pancreatic lipase interact with one calcium ligand. A close look at the <scene name='Sandbox_44/Contacts_of_calcium/1'>contacts of calcium</scene> shows these calcium ligands to be located between the acidic residues Glu, Arg, and Asp. These four residues (Glu 187, Arg 190, Asp 195, and Asp 192) interact specifically with the calcium ligand in each chain. | <p> Each of the two chains of pancreatic lipase interact with one calcium ligand. A close look at the <scene name='Sandbox_44/Contacts_of_calcium/1'>contacts of calcium</scene> shows these calcium ligands to be located between the acidic residues Glu, Arg, and Asp. These four residues (Glu 187, Arg 190, Asp 195, and Asp 192) interact specifically with the calcium ligand in each chain. | ||
</p> | </p> | ||
| - | Within the lipase molecule there are various hydrophilic (polar) and hydrophobic residues to account for the molecules amphiphilic properties, where stability within the molecule in both polar and non polar environments is of utmost importance. The <scene name='Sandbox_44/Hydrophobic_residues/1'>hydrophobic residues</scene> of pancreatic lipase can be seen here in grey, while the polar residues of pancreatic lipase are shown in purple. Again, a fairly even distribution of polar to nonpolar residues are seen so as to most effectively stabilize the molecule under whatever conditions are encountered in digestion. | + | Within the lipase molecule there are various hydrophilic (polar) and hydrophobic residues to account for the molecules amphiphilic properties, where stability within the molecule in both polar and non polar environments is of utmost importance. All of triacylglycerol digestion occurs at lipid-water interfaces; therefore, it is easy to understand why lipase must be stable in either environment. The <scene name='Sandbox_44/Hydrophobic_residues/1'>hydrophobic residues</scene> of pancreatic lipase can be seen here in grey, while the polar residues of pancreatic lipase are shown in purple. Again, a fairly even distribution of polar to nonpolar residues are seen so as to most effectively stabilize the molecule under whatever conditions are encountered in digestion. |
<p> | <p> | ||
</StructureSection> | </StructureSection> | ||
Revision as of 03:27, 14 November 2011
| Please do NOT make changes to this Sandbox. Sandboxes 30-60 are reserved for use by Biochemistry 410 & 412 at Messiah College taught by Dr. Hannah Tims during Fall 2012 and Spring 2013. |
Contents |
Lipase
PDB ID: 1HPLE.C.: 3.1.1.3
Number of Amino Acid Residues: 449
Number of Chains: 2
Weight: 50kDa
Introduction
The lipase class of enzymes are known to cut a lipid substrate at a specific location on their glycerol backbone. Lipase catalyzes the lipid breakdown through the hydrolysis of the esters in fatty acids. While lipase is found primarily in the human pancreas, lipase can also be located in other areas in the body such as the mouth and the stomach. Pancreatic lipase, in particular, serves in human digestion to break down fats from the human diet. This lipase, therefore, is found in the digestive system of humans and is involved in the conversion of triglycerides to monoglycerides and free fatty acids.Human pancreatic lipase distinguishes itself from other pancreatic enzymes because when it is synthesized it is done so in its final form, without needing to be activated through proteolytic cleavage. However, while lipase does not need outside activation, it is not truly efficient without the presence of colipase in the duodenum.
The crystal structure of human pancreatic lipase is still yet to be determined and the research goal of many current scientists. Therefore, the structure examined here, 1HPL, is in actuality horse pancreatic lipase, thought to have a very similar structure as well as function with regard to human pancreatic lipase.
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