Bharati K, Hasson S S, Oliver J, Laing G D, Theakston R D G, Harrison R A
Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK.
Toxicon. 2003 Jun;41(8):941-7. doi: 10.1016/s0041-0101(02)00312-4.
Venom toxin-specific antibodies offer a more rational treatment of snake envenoming than conventional antivenom. Here, we describe novel cDNAs encoding phospholipase A(2) (PLA(2)) isoforms from venom gland RNA of Echis pyramidum leakeyi (Epl), Echis sochureki (Es) and Echis ocellatus (Eo). The deduced amino acid sequences of these cDNAs encoded proteins with high overall sequence identity to the viper group II PLA(2) protein family, including the 14 cysteine residues capable of forming seven disulphide bonds that characterize this group of PLA(2) enzymes. Comparison of the PLA(2) sequences from Echis with those from related vipers failed to make significant geographic, taxonomic or PLA(2)-function distinctions between these Echis PLA(2) isoforms. However, their deduced hydrophilicity profiles revealed a conserved tertiary structure that we will exploit, by epidermal DNA immunization, to generate PLA(2)-neutralizing antibodies with polyspecific potential.
毒液毒素特异性抗体比传统抗蛇毒血清能更合理地治疗蛇咬伤中毒。在此,我们描述了从锯鳞蝰(Echis pyramidum leakeyi,Epl)、索氏锯鳞蝰(Echis sochureki,Es)和眼斑锯鳞蝰(Echis ocellatus,Eo)的毒腺RNA中编码磷脂酶A2(PLA(2))同工型的新cDNA。这些cDNA推导的氨基酸序列编码的蛋白质与蝰蛇II组PLA(2)蛋白家族具有高度的整体序列同一性,包括能够形成七个二硫键的14个半胱氨酸残基,这是该组PLA(2)酶的特征。将锯鳞蝰的PLA(2)序列与相关蝰蛇的序列进行比较,未能在这些锯鳞蝰PLA(2)同工型之间做出显著的地理、分类或PLA(2)功能区分。然而,它们推导的亲水性图谱揭示了一种保守的三级结构,我们将通过表皮DNA免疫利用该结构来产生具有多特异性潜力的PLA(2)中和抗体。