绿脓杆菌外毒素A有三个结构功能区.氨基端区(Ⅰ)通过关键位点Lys57结合靶细胞表面受体.中心区(Ⅱ)负责该毒素的跨膜转位功能,Arg276和Arg279是关键位点.在胞吞泡内此毒素于Arg279与Gly280间酶解成28 000和37 000两片段.羧基端区(Ⅲ)所在的37 000片段由其末端氨基酸序列REDLK介导到内质网再转位入胞浆通过Glu553位点结合NAD+使延伸因子-2受ADP-核糖基化而抑制细胞蛋白质合成导致细胞死亡.改造的毒素基因同识别蛋白基因融合成的重组毒素有应用前景.
Pseudomonas aeruginosa exotoxin A(PE)contains three structure function domains. The amino-terminal domain Ⅰ is involved in binding to target cell-surface receptors through the active site Lys57.The central domain Ⅱ is responsible for the translocation of PE across membranes,Arg276 and Arg279 are the active key positions of the domain Ⅱ.The protease cleaves PE between Arg279 and Gly280 into 28 000 and 37 000 fragments. The carboxyl-terminal domain Ⅲ is located in 37 000 fragment which is directed by the REDLK sequence at the carboxyl end of domain Ⅲ to the endoplasmic reticulum and translocated to the cytosol, and then ADP-ribosylates the EF-2 (elongation factor 2) by binding NAD+ through the key site Glu553 to result in the inhibition of cell protein synthesis and death of target cells. It is a practical prospect that the recombinant immunotoxins are made by fusing DNA fragments encoding recognition proteins to the modified PE genes.
杜世彧.绿脓杆菌外毒素A的结构、功能及其重组毒素[J].生物化学与生物物理进展,1995,22(2):112-117
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