Possani L D, Zurita M, Delepierre M, Hernández F H, Rodríguez M H
Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca.
Toxicon. 1998 Nov;36(11):1683-92. doi: 10.1016/s0041-0101(98)00161-5.
This communication reviews shortly the main structural and functional characteristics of Noxiustoxin, a 39 amino acid residue peptide, maintained closely packed by three-disulfide bridges and its effects on excitable membranes. Shiva-3, a cecropin like-peptide composed of 38 amino acid residues is also briefly reviewed. Its design and synthesis was made possible by the expertise gained through the work previously performed with Noxiustoxin. One of the most prominent functional characteristics of Shiva-3 is the toxic effect upon the sporogonic development of Plasmodium berghei (responsible for a murine version of malaria). A synthetic Shiva-3 gene was constructed by recursive polymerase-chain reaction (PCR) methodology and expressed using the vector pGEX2T as a hybrid protein between the glutathione-S-transferase at the N-terminal and Shiva-3 in the C-terminal part of the hybrid. The recombinant protein kills bacteria and Plasmodium berghei. The future aim of this work is to produce a transgenic mosquito that carries the message for synthesis and excretion of Shiva-3 and similar peptides, in the midgut of mosquitoes, in an attempt to control the spreading of human malaria.
本通讯简要回顾了诺西毒素（一种由39个氨基酸残基组成的肽，通过三个二硫键紧密结合）的主要结构和功能特征及其对可兴奋膜的影响。还简要回顾了 Shiva-3，一种由38个氨基酸残基组成的类似杀菌肽的肽。它的设计和合成得益于之前对诺西毒素研究积累的专业知识。Shiva-3最显著的功能特征之一是对伯氏疟原虫（引发鼠疟）孢子生殖发育的毒性作用。通过递归聚合酶链反应（PCR）方法构建了合成的Shiva-3基因，并使用载体pGEX2T进行表达，使其作为一种杂合蛋白，N端为谷胱甘肽-S-转移酶，C端为Shiva-3。重组蛋白可杀死细菌和伯氏疟原虫。这项工作未来的目标是培育一种转基因蚊子，使其在蚊子中肠携带合成和分泌Shiva-3及类似肽的信息，以尝试控制人类疟疾的传播。
