Carredano E, Westerlund B, Persson B, Saarinen M, Ramaswamy S, Eaker D, Eklund H
Department of Molecular Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Toxicon. 1998 Jan;36(1):75-92. doi: 10.1016/s0041-0101(97)00051-2.
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.
已分别以2.2埃和3.0埃的分辨率测定了来自罗素蝰蛇（Vipera russelli russelli）毒液的II类抗凝磷脂酶A2（PLA2）毒素RVV - VD以及来自澳大利亚虎蛇（Notechis scutatus scutatus）的I类神经毒性PLA2诺氏毒素II - 5的三维结构。这两种酶均为单体，分别由121个和119个残基组成。对十种I/II类PLA2结构的比较显示，除其他差异外，这些酶的β折叠（残基76 - 83）在I类中比在II类PLA2中扭曲程度小约90度。这一点，连同I类酶中57 - 59区域（眼镜蛇环）中一些残基的插入，可能是这两类PLA2在抗凝和（突触前）神经毒性特性上存在显著差异的主要原因。从序列和结构比较中似乎可以明显看出，PLA2中负责这些毒素强抗凝性的毒性位点由带负电荷的部分Glu53以及可供分子间相互作用的带正电荷的赖氨酸残基脊组成。这两类PLA2中的这些赖氨酸有所不同。
