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

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 Angstrom and 3.0 Angstrom 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 beta-sheet of these enzymes (residues 76-83) is about 90 degrees 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). (C) 1998 Elsevier Science Ltd. All rights reserved.