THE 3-DIMENSIONAL STRUCTURES OF 2 TOXINS FROM SNAKE-VENOM THROW LIGHTON THE ANTICOAGULANT AND NEUROTOXIC SITES OF PHOSPHOLIPASE A(2)

The three-dimensional structures of the class II anticoagulant phospho lipase A(2) (PLA(2)) toxin RVV-VD from the venom of Russell's viper, V ipera russelli russelli, and the class I neurotoxic PLA(2) Notechis II -5 from the Australian tiger snake, Notechis scutatus scutatus, were d etermined to 2.2 Angstrom and 3.0 Angstrom resolution, respectively. B oth enzymes are monomeric and consist of 121 and 119 residues, respect ively. A comparison of ten class I/II PLA(2) structures showed, among other differences, that the beta-sheet of these enzymes (residues 76-8 3) 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 th e significant difference in the anticoagulant and (presynaptic) neurot oxic properties between the two classes of PLA(2). It seems apparent f rom 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 Sc ience Ltd. All rights reserved.