α-鹅膏毒肽与真核生物RNA聚合酶Ⅱ相互作用研究进展

Research progress on the interaction betweenα-amanitin and eukaryotic RNA polymeraseⅡ

鹅膏毒肽是我国蘑菇中毒事件中致死率最高的蘑菇毒素。鹅膏毒肽引起机体中毒的主要机制为鹅膏毒肽与真核生物RNA聚合酶Ⅱ(RNAPⅡ)特异性结合并抑制mRNA形成。本文系统整理了有关α-鹅膏毒肽与真核生物RNAPⅡ相互作用的国内外研究进展。由于同一时代各领域对该主题有不同研究角度,研究进展既有平行也有交叉,因此,本文将鹅膏毒肽与真核生物RNAPⅡ相互作用的110多年研究史(1907–至今)分为8个阶段,包括(1)鹅膏毒肽的早期研究、(2)化学结构解析、(3)毒理学研究、(4)构-效关系研究、(5)生物化学研究、(6)分子生物学研究、(7)结构生物学研究和(8)药物开发与评价。本文按以上顺序,分主题论述α-鹅膏毒肽与真核生物RNAPⅡ相互作用的研究历程和重要研究结果,以期给中毒和临床毒理学等领域带来新的思考。

Amanitin is the most lethal mushroom toxin in mushroom poisoning cases in China.The main mechanism of amanitin poisoning is the interaction between amanitin and eukaryotic RNA polymeraseⅡand inhibiting the formation of mRNA.In this paper,the research progress concerning interaction betweenα-amanitin and eukaryotic polymeraseⅡwas reviewed.The research history of 110 years(1907–)of interaction betweenα-amanitin and eukaryotic polymeraseⅡis divided into eight stages,including early research on amanitins,advancement of chemical structure analysis,toxicology research,structure-activity relationship research,biochemistry research,molecular biology research,structural biology research,and drug development and evaluation.The corresponding discussion on research processes and important results is given.Hopefully this paper will bring new thinking to the field of clinical toxicology.