Structure-Function Relationship in Heterodimeric Neurotoxin PLA2s from Viperidae Snakes Inhabiting Europe, South America, and Asia Functional Importance of the Nontoxic Components

Snake venom heterodimeric non-covalent phospholipase A(2) (PLA(2)) complexes (ncHdPLA(2)s) are neurotoxins encountered in the venoms of Viperinae and Crotalinae snakes. In contrast to their monomeric counterparts, they have a sophisticated mechanism of action in order to avoid nonspecific binding to wrong targets and to increase the efficiency of the pharmacological attack. ncHdPLA(2)s consist of a toxic and enzymatically active basic PLA(2) and an acidic and catalytically inactive PLA(2) protein. The main function of the acidic subunit is to direct the toxic component to the correct targets on the cell membrane and in this way to avoid binding to phospholipids, which are not important for the pharmacological effect of the toxin. The nontoxic component of ncHdPLA(2)s is multifunctional. It can modulate the toxicity and catalytic activity of PLA(2). The structure and function of ncHdPLA(2)s from the venoms of snakes inhabiting Europe, South America, and Asia are similar. There exists a high identity at the levels of primary and three-dimensional structures of ncHdPLA(2)s from snakes inhabiting widely separated regions of the world. Although a substantial progress has been made during the last years in understanding the structure and biological action of ncHdPLA(2)s, a number of questions still remain to be answered.