Facing up to Membranes: Structure/Function Relationships in Phospholipases

Abstract

Phospholipases are unique enzymes in that they have evolved to attack aggregated substrates (e.g., phospholipids in a membrane). Only a trace of their full activity is exhibited against monomerically dispersed phospholipids. Moreover, phospholipase activity can be “tuned” by structural factors operating within the aggregate. These include steric influences on the head groups, hydration of the polar regions, chain-packing density, surface charge, and surface defects, all of which contribute to the physical state of the interfacial region (for review, see Israelachvili et al. 1980). Furthermore, perturbation of lamellar aggregates by insertion of amphipathic proteins may modulate phospholipase activity. For example, amphipathic peptides such as melittin from bee venom (Vogel 1981), cardiotoxins from some snake (Elapidae) venoms (Louw and Visser 1978), and polymixin B (bacterial), which are known to insert into phospholipid bilayers, increase the activity of extracellular phospholipases A2 toward phospholipid vesicles, liposomes (Yunes et al. 1977), and cell membranes (Tönsing...