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 A2 (PLA2) toxin RVV-VD from the venom of Russell's viper, Vipera russelli russelli, and the class I neurotoxic PLA2 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 PLA2 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 PLA2s. 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 PLA2. It seems apparent from sequence and structural comparisons that the toxic site of PLA2 responsible for the strong anticoagulancy of these toxins consists of a negatively charged part, Glu53, together with a positively charged ridge of lysine residues free for intermolecular interactions. These lysines differ between the two classes of PLA2.
Carredano
E
E
Department of Molecular Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Westerlund
B
B
Persson
B
B
Saarinen
M
M
Ramaswamy
S
S
Eaker
D
D
Eklund
H
H
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000737:chemistry*; D001665:Binding Sites; D003461:Crystallography; D004546:Elapid Venoms / Q000737:chemistry / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry*; D010741:Phospholipases A / Q000737:chemistry*; D054467:Phospholipases A2; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000201:enzymology*
D000925:Anticoagulants; D004546:Elapid Venoms; D009498:Neurotoxins; D014757:Viper Venoms; C005082:notexin; D010741:Phospholipases A; D054467:Phospholipases A2