Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes.
Venom phospholipase A2 (PLA2) enzymes share similarity in structure and catalytic function with mammalian enzymes. However, in contrast to mammalian enzymes, many are toxic and induce a wide spectrum of pharmacological effects. Thus structure-function relationship of this group of small proteins is subtle, but complex puzzle to protein biochemists, molecular biologists, toxinologists, pharmacologists and physiologists. This review describes the present status of our understanding of their structure, function and mechanism. It was proposed that their unique ability to 'target' themselves to a specific organ or tissue is due to their high affinity binding to specific proteins which act as receptors (more precisely, acceptors). This specific binding of PLA2 is conferred by the presence of a 'pharmacological site' on its surface which is independent of the catalytic site. The high affinity interaction of PLA2 with its acceptor (or target protein) is probably due to the complementarity, in terms of charges, hydrophobicity and van der Waal's contact surfaces, between the pharmacological site and the binding site on the surface of the acceptor protein. Upon binding to the target, the PLA2 can induce its pharmacological effects by mechanisms either dependent on or independent of its catalytic activity. Because of the unprecedented wide spectrum of specific targeting to various tissues and organs, identification of the pharmacological sites has potential for exploitation in development of novel systems useful for 'delivering' specific proteins to a particular target tissue or organ. Thus research in this field will provide a lot of exciting opportunities.
Kini
R Manjunatha
RM
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117543. dbskinim@nus.edu.sg
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D008956:Models, Chemical; D010741:Phospholipases A / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D054467:Phospholipases A2; D012910:Snake Venoms / Q000201:enzymology*; D012911:Snakes; D013329:Structure-Activity Relationship
D012910:Snake Venoms; D010741:Phospholipases A; D054467:Phospholipases A2