The three-dimensional structures of two toxins from snake venom throw light on the anticoagulant and neurotoxic sites of phospholipase A2.

Abstract The three-dimensional structures of the class II anticoagulant phospholipase A 2 (PLA 2 ) toxin RVV-VD from the venom of Russell's viper, Vipera russelli russelli , and the class I neurotoxic PLA 2 Notechis II-5 from the Australian tiger snake, Notechis scutatus scutatus , were determined to 2.2 A and 3.0 A resolution, respectively. Both enzymes are monomeric and consist of 121 and 119 residues, respectively. A comparison of ten class I/II PLA 2 structures showed, among other differences, that the β -sheet of these enzymes (residues 76–83) is about 90° less twisted in class I than in class II PLA 2 s. This, along with the insertion of some residues in the region 57–59 in class I enzymes (the elapid loop), could be the main reason for the significant difference in the anticoagulant and (presynaptic) neurotoxic properties between the two classes of PLA 2 . It seems apparent from sequence and structural comparisons that the toxic site of PLA 2 responsible for the strong anticoagulancy of these toxins consists of a negatively charged part, Glu 53 , together with a positively charged ridge of lysine residues free for intermolecular interactions. These lysines differ between the two classes of PLA 2 .