Inhibition of human group IIA Phospholipase A2 by Petrosaspongiolide M through a mechanism of protein-protein trans-inactivation

MONTI, MARIA C.; CAVASOTTO, CLAUDIO N.; TOSCO, A.; DAL PIAZ, F.; LEONE, A.; CASAPULLO, A.; RICCIO, R.; ABAGYAN, RUBEN A.; GOMEZ-PALOMA, LUIGI

ATLANTA, GA

Conferencia; 231st National Meeting of the American-Chemical-Society; 2006

Phospholipases A2 (PLA2) play a key role in the metabolism of phospholipids cleaving the sn-2 ester bond of membrane in a regiospecific and stereospecific manner. Mammalian tissues contain both secretory (sPLA2s) and cytosolic enzymes, which require Ca2+ as catalytic ion. Human type-IIA secreted PLA2 (sPLA2-IIA) results to be inactive on the monomeric phospholipid substrate; its activity discloses only on phospholipid layers by means of a phenomenon called "interfacial activation". Monolayers, micelles, vesicles and membranes are some of its supramolecular species preferentially hydrolyzed. The region of sPLA2-IIA that interacts with extra-cellular membranes, called interfacial binding surface (IBS), involves mainly hydrophobic residues, two basic residues, a single acidic and neutral amino acid, all stuck on the phospholipid layers. In addition, K67 and K107 lie 4-5 Å from the surface.