Structure-Function Relationship in Heterodimeric Neurotoxin PLA2s from Viperidae Snakes Inhabiting Europe, South America, and Asia
Snake venom heterodimeric non-covalent phospholipase A2 (PLA2) complexes (ncHdPLA2s) 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. ncHdPLA2s consist of a toxic and enzymatically active basic PLA2 and an acidic and catalytically inactive PLA2 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 ncHdPLA2s is multifunctional. It can modulate the toxicity and catalytic activity of PLA2.
The structure and function of ncHdPLA2s 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 ncHdPLA2s 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 ncHdPLA2s, a number of questions still remain to be answered.
KeywordsSnake Venom Presynaptic Membrane Basic Subunit Acidic Subunit PLA2 Component
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