InterPro domain: IPR036444

Proteins containing this domain superfamily include eukaryotic and prokaryotic phospholipase A2 enzymes (PLA2; 3.1.1.4 ), small lipolytic enzymes that releases fatty acids from the second carbon group of glycerol, usually in a metal-dependent reaction, to generate lysophospholipid (LysoPL) and a free fatty acid (FA) [ 1 ]. The resulting products are either dietary or used in synthetic pathways for leukotrienes and prostaglandins. Often, arachidonic acid is released as a free fatty acid and acts as second messenger in signaling networks [ 2 ]. These enzymes enable the of fatty acids and lysophospholipid by hydrolysing the 2-ester bond of 1,2-diacyl-3-sn-phosphoglycerides. In eukaryotes, PLA2 plays a pivotal role in the biosynthesis of prostaglandin and other mediators of inflammation. These enzymes are either secreted or cytosolic; the latter are either Ca dependent or Ca independent. Secreted PLA2s have also been found to specifically bind to a variety of soluble and membrane proteins in mammals, including receptors [ 3 ]. As a toxin, PLA2 is a potent presynaptic neurotoxin which blocks nerve terminals by binding to the nerve membrane and hydrolyzing stable membrane lipids [ 4 ]. The products of the hydrolysis (LysoPL and FA) cannot form bilayers leading to a change in membrane conformation and ultimately to a block in the release of neurotransmitters [ 5 , 6 , 7 ].

The phospholipase domain adopts an alpha-helical secondary structure, consisting of five alpha-helices and two helical segments. PLA2 may form dimers or oligomers [ 8 , 9 , 10 ].

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2. Regulation and inhibition of phospholipase A2. Annu. Rev. Pharmacol. Toxicol. 39, 175-89
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4. Modulation of phospholipase A2 activity generated by molecular evolution. Cell. Mol. Life Sci. 56, 384-97
5. Presynaptic enzymatic neurotoxins. J. Neurochem. 97, 1534-45
6. How do presynaptic PLA2 neurotoxins block nerve terminals? Trends Biochem. Sci. 25, 266-70
7. Equivalent effects of snake PLA2 neurotoxins and lysophospholipid-fatty acid mixtures. Science 310, 1678-80
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10. Crystal structure of human group X secreted phospholipase A2. Electrostatically neutral interfacial surface targets zwitterionic membranes. J. Biol. Chem. 277, 29086-93