绿脓杆菌外毒素A的结构、功能及其重组毒素

Structure and Function of Pseudomonas aerug-inosa Exotoxin A and Its Recombinant Toxin.

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２８０００和３７０００两片段。羧基端区（Ⅲ）所在的３７０００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 exotoxinA(PE)contains three structure function do-mains. The amino-terminal domain Ⅰ is in-volved in binding to target cell-surface recep-tors through the active site Lys57.The cen-tral domain Ⅱ is responsible for the transloca-tion of PE across membranes,Arg276 andArg279 are the active key positions of the do-main Ⅱ.The protease cleaves PE betweenArg279 and Gly280 into 28 000 and 37 000fragments. The carboxyl-terminal domain Ⅲis located in 37 000 fragment which is directedby the REDLK sequence at the carboxyl endof domain Ⅲ to the endoplasmic reticulum andtranslocated to the cytosol,and then ADP-ri-bosylates the EF-2(elongation factor 2)bybinding NAD￣+ through the key site Glu553 toresult in the inhibition of cell protein synthesisand death of target cells.It is a practicalprospect that the recombinant immunotoxinsare made by fusing DNA fragments encodingrecognition proteins to the modified PE genes.