Structural Aspects of Lipase
The structure of lipase displays the enzyme in its natural form, with its two identical chains, each consisting of 449 amino acid residues. The secondary structures 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 hydrogen bonds can be seen throughout the structure of lipase, displayed here in bright yellow for clarity.
There are two main chains in human pancreatic lipase, shown here as Chain A and Chain B. Chain A (in blue) is exactly identical to Chain B (in green), and each chain has two domains which can be identified through N terminus to C terminus labeling. 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.
The active site of Chain A 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.
The identical active site of Chain B is shown here in red, also facilitating the reaction, the mechanism of which will be discussed below.
Each of the two chains of pancreatic lipase interact with one calcium ligand. A close look at the contacts of calcium 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.
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 hydrophobic residues 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.
