Regulation of Pancreatic Phospholipase A₂ Activity by Different Lipid-Water Interfaces

Summary

Pancreatic phospholipase A₂ interacts with lipid-water interfaces by means of a specific region, the Interface Recognition Site (IRS), which most probably penetrates to a certain extent into the hydrophobic interior of the lipid phase. This process causes a dramatic increase in the rate of hydrolysis. The IRS embraces at least the rather apolar N-terminal sequence of the polypeptide chain: Ala. Leu. Trp. Gln. Phe. Arg. Ser. Met and its most effective configuration seems to be stabilised by an ionpair between the $\alpha -\overset{+}{\mathop{N}}\,{{H}_{3}}$ group of the N-terminal amino acid Ala and a buried carboxylate function.

Using a series of specifically modified phospholipases,in which the native N-terminal amino acid L-Ala has been deleted or substituted by other amino acids, the properties of the IRS were compared by spectroscopic techniques and monolayer kinetics..

Substitution of L-Ala by Gly or ?-Ala does not seriously impede the penetrating properties of the enzyme. Chain elongation, chain shortening or even replacement of L-Ala by D-Ala, however, weakens the IRS in such a manner, that penetration of the relatively close-packed micelles becomes impossible. These enzymes still interact with monomolecular surface films up to well-defined surface pressures.