細菌之核苷核糖化毒素：綠膿桿菌外毒素A

ADP-Ribosylating Bacterial Toxins: Pseudomonas Exotoxin A

陳作琳(Tso-Ling Chen) ； 林立中(Lee-Chung Lin) ； 黃昭蓮(Jau-Lang Hwang) ； 林嘉伯(Chia-Po Lin)

《藥物食品分析》 4卷2期 (1996/06) Pp. 107-114

摘要

對於一些細菌所產生的毒素，經由作用於眞核細胞內某些重要蛋白質的核苷核糖化反應(ADP-ribosylating reaction)而影響其正常的生理功能已有大致的了解。大部份這類的毒素主要是由兩個部份(moieties)，A和B所組成。B部份負責其分子本身與毒性敏感細胞表面特殊受器的結合，而A部份則負責執行核苷核糖化(ADP-ribosylate)細胞內蛋白質的酵素活性。綠膿桿菌外毒素A （Pseudomonas、exotoxin A，簡稱PEA），是綠膿桿菌所產生的細胞外產物中最具毒性的成份。此一外泌性蛋白質毒素主要由三個區域(domains)所組成：即區域Ⅰ，區域Ⅱ和區域Ⅲ，其主要功能分別與細胞的結合(binding)、在細胞內的移位(translocation)和發揮核苷核糖化活性(ADP-ribosylating activity)有關。吾人若應用綠膿桿菌外毒素A之核苷核糖化反應毒殺細胞的功能，一般皆相信可以作為製備免疫毒素(immunotoxins)的最佳選譯。在本篇綜論中，吾人將討論核苷核糖化細菌毒素(ADP-ribosylating bacterial toxin)的結構、作用機制，並對於綠膿桿菌外毒素A，以及綠膿桿菌外毒素A和其他核苷核糖化毒素(ADP-ribosylating toxin)的異同作一簡介。

關鍵字

核苷核糖化 ； 細菌毒素 ； 綠膿桿菌外毒素A

並列摘要

It is well known that a number of toxins produced by bacteria exert their action by ADP-ribosylating reaction to certain proteins which are essential for normal eukaryotic cellular functions. Most of these toxins are composed of two moieties, A and B. The B moiety mediates the binding to the specific receptor on the surface of toxin-sensitive cells, while the A moiety is responsible for the enzymatic ADP-ribosylating activity. Pseudomonas exotoxin A (PEA) is the most toxic component of the extracellular prod ucts produced by Pseudomonas aeruginosa. The three domain model of PEA has been well established domain Ⅰ, domain Ⅱ, and domain Ⅲ exerting binding, translocation, and ADP-ribosylating activities, respectively. Because of the cytotoxic ADP-ribosylating nature of PEA, it has been suggested as a good candidate in the preparation of immunotoxins. In this minireview article, we discuss the structure and function of the bacterial ADP-ribosylating toxins including PEA and compare the differences particularly between PEA and other valevant toxins.

並列關鍵字

ADP-ribosylation ； bacterial toxins ； Pseudomonas exotoxin A PEA