Phospholipases : evolution of catalytic and cellular functions at the membrane level

The inflammatory cascade is initiated by the release of free arachidonic acid by a type of phospholipase_A2, belonging to a super-family of enzymes interacting with membrane phospholipids. The phospholipase_A2 (PLA2) super-family is made up of 16 groups and numerous sub-groups, constituting a diverse set of enzymes sharing a common catalytic activity due to their convergent evolution. Nevertheless, the different types of PLA2 have unique three-dimensional structures and catalytic residues, as well as specific tissue localization, biological functions and unique allosteric interactions with membranes. In recent years, a mass spectrometry approach focusing on hydrogen/deuterium isotope exchange has led to a better understanding of how different PLA2s associate with phospholipid membranes, and of their specific substrates and molecular inhibitors.