細菌之核苷核糖化毒素：綠膿桿菌外毒素A   全文下載

ADP-Ribosylating Bacterial Toxins Pseudomonas Exotoxin A

對於一些細菌所產生的毒素，經由作用於真核細胞內某些重要蛋白質的核?核糖化反應（ADP-ribosylatingreaction）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?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 exotoxinA，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?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?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）的最佳選擇。在本篇綜論中，吾人將討論核?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?核糖化毒素（ADP-ribosylating toxin）的異同作一簡介。

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 products 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.