Structure of porcine pancreatic prephospholipase A2

PHOSPHOLIPASE A 2 (EC 3.1.1.4) catalyses the hydrolysis of the fatty acid ester bond at the 2-position of 1,2 diacyl sn-phosphoglycerides, and has been purified from many sources, such as mammalian pancreas 1,2 , snake venom 3 and bee venom 4 . In mammals, the enzyme is produced as a precursor, which trypsin can convert into active phospholipase A 2 by splitting the peptide bond Arg 7–Ala 8, with the removal of the N -terminal heptapeptide from the molecule 5 . The activity of the different phospholipases A 2 depends on the physical state of the substrate. The enzyme from snake venom is highly active when the substrate is tightly packed in a membrane. Mammalian phospholipases cannot attack membranes; they can degrade the lecithin molecules most effectively when these are more loosely packed in micelles. All phospholipases also have some activity towards substrates in a monomeric solution. The precursors from mammalian pancreas phospholipases are also active towards the monomeric substrate molecules, but inactive to substrates in micellar form 6 . The primary structure of many of the phospholipases A 2 is known. They have a single polypeptide chain of approximately 130 amino acid residues and six or seven disulphide bridges 7–10 . There is a high degree of homology between all the enzymes. We report here the three-dimensional structure of one of these enzymes, prephospholipase A 2 from porcine pancreas.