Conodipine-P1-3, the First Phospholipases A₂ Characterized from Injected Cone Snail Venom

The phospholipase A₂ (PLA₂s) superfamily are ubiquitous small enzymes that catalyze the hydrolysis of phospholipids at the sn-2 ester bond. PLA₂s in the venom of cone snails (conodipines, Cdpi) are composed of two chains termed as alpha and beta subunits. Conodipines are categorized within the group IX of PLA₂s. Here we describe the purification and biochemical characterization of three conodipines (Cdpi-P1, -P2 and -P3) isolated from the injected venom of Conus purpurascens Using proteomics methods, we determined the full sequences of all three conodipines. Conodipine-P1-3 have conserved consensus catalytic domain residues, including the Asp/His dyad. Additionally, these enzymes are expressed as a mixture of proline hydroxylated isoforms. The activities of the native Conodipine-Ps were evaluated by conventional colorimetric and by MS-based methods, which provide the first detailed cone snail venom conodipine activity monitored by mass spectrometry. Conodipines can have medicinal applications such inhibition of cancer proliferation, bacterial and viral infections among others.