Colipase-binding

The /1-sandwich C-terminal domain of pancreatic lipase is necessary for colipase binding to occur, as shown in the 3-D structure of the HPL-porcine procolipase... 

Figure 2 Structure of human pancreatic lipase with indication of the active site buried beneath a mobile Trp 252 surface loop (flap) in order to give access to the substrate and the colipase-binding site faced in the same direction as the active site. The enzyme is glycosylated at Asn 166 (porcine), stabilized at the surface segment by a Ca2+-binding site (partly hidden, marked by an asterisk), and can be anchored by means of the heparin-binding site to heparan sulfate on cell surfaces. (From Ref. 8.)...

As illustrated in Figure 2, human pancreatic lipase consists of two domains. The larger N-terminal domain, a mixed 0E,P-stmcture, comprises residues 1-335 and contains the catalytic triad and a calcium-banding site. The smaller C-terminal domain is formed by two layers of antiparallel -strands and presents a binding site for colipase. 

Bezzine, S., Ferrato, F., Ivanova, M.G., Lopez, V., Verger, R. and Carriere, F. (1999) Human pancreatic lipase colipase dependence and interfacial binding of lid domain mutants. Biochemistry 38, 5499-5510. 

Pancreatic lipase is the primary digestive enzyme for the breakdown of triglycerides. It acts on triglycerides to hydrolyze the fatty acyl ester bonds. Lipase is specific for the ester bonds in the V- and 3 -positions to produce free fatty acids and P-monoacylglycerols. Pancreatic lipase is strongly inhibited by bile acids and therefore requires the presence of colipase, a small protein that binds to the lipase and activates it. 

The exocrine pancreas secretes phospholipase A2 in an inactive zymogen form, prophospholipase A2. The enzyme is activated in the intestinal lumen by proteolytic cleavage by trypsin. Pancreatic lipase, however, is secreted in its active form, and only needs to bind colipase and substrate to be active. 

J, S, Patton, P, A. Albertsson, C. Erlanson. B, Borstrom. Binding of porcine pancreatic lipase and colipase in the absence of substrate studied by 2-phase partition and affinity cfiromaiography. J Biol Chem 253 4195-4202. 1978. 

Signals in the aromatic region of the n.m.r. spectrum of colipase have been assigned to L-histidine residues. L-Histidine C-2 proton signals have been used in studies of the binding to ribonuclease A of H, edta and of 2 -deoxy-2 -fluorouridilyl-(3, 5 )-adenosine. L-Phenylalanine, L-tyrosine, and methionine side-chain proton resonances were used as monitors for the unfolding and stabilization of ribonuclease." ... 

---