Sandbox 48

Lipase is an enzyme the body uses to break down fats during digestion. Primarily secreted by the pancreas, but also found in the mouth and stomach, this enzyme is just one of the many enzymes secreted into the duodenum to break down food. Due to its environment, this enzyme is water soluble and can work in various pHs. Shown here is the elucidated structure of horse pancreatic enzyme. It has been found to be very similar to human pancreatic enzyme and has been used to better understand the human enzyme.

Structure

Lipase has two domains. The N-terminal domain, which contains the , has typical alpha/beta-hydrolase fold and makes up two thirds of the molecule. This means that it shares with several other enzymes such as acetylcholinesterase, dienelactone hydrolase, thioesterase, and serine carboxypeptidase and many others, the same structure around its active site (Holmquist, 2000). The is representative of the serine proteases. It is covered by a hydrophobic flap to protect it from solvent molecules. Opening of the flap allows access for the substrate to the catalytic site, the oxyanionic hole, and strengthened binding of collipase (Borne et al., 1994).

The C terminal domain is responsible for binding to colipase, a small protein responsible for binding on to the inhibiting bile salt coated lipid-water interface. Without binding to colipase,lipase would not be able to catalyze the digestion of lipids because of the strong inhibitory effect of bile salts. This domain has a beta-sandwhich type morphology, made by four anti-parallel strands that allow for both hydrophobic and ionic binding of colipase. This domain also has an active site that hydrolyses p-nitrophenyl-acetate that is irreversibly acetylated on a lysyl residue (Holmquist, 2000).

References

Holmquist, M. Alpha/Beta-hydrolase fold enzymes: structures, functions and mechanisms.Curr Protein Pept Sci. 2000 Sep;1(2):209-35.

Bourne, Y; Martinez, C; Kerfelec, B; Lombardo, D; Chapus, C; Cambillau, C. Horse pancreatic lipase. The crystal structure refined at 2.3 A resolution. J Mol Biol. 1994 May 20;238(5):709-32.