不同有机磷酸酯磷酰化乙酰胆碱酯酶活性中心的构象差异

通过观察2位肟化合物HI-6和HGG-42及它们的4位胎异构体对不同有机磷毒剂抑制的AChE的重活化作用发现塔崩、梭曼、沙林等有机磷毒剂磷酰化的AChE活性中心的构象可能存在着明显差异;又从变构剂C₁₀和丙吡啶对TMB₄重活化这几种毒剂磷酰化AChE的影响中证实塔崩磷酰化AChE活性中心构象与沙林、梭曼和VX3种毒剂磷酰化的AChE明显不同.

Evidences of Conformational Difference in the Active Centre of Phosphorylated Acetylcholinesterases

The striking distinctions ofoximes. such as 2-PAM,LuH6,TMB_4 andHI-6. in reactivating sarin-,soman-,tabun-and VX- phosphorylated acetylcholinesterase(AChE)imply that there are factors whichhinder phosphorylated enzymes from being re-activated by some oximes before aging. To in-vestigate this phoblem,a comparison of invitro reactivation of these phosphorylated en-zymes by H series oximes,HI-6,HGG-42 andtheir 4-oxime isomers.was made. Resultsshowed that,in tabun experiments,althoughthere was no reactivation by the two 2-oximes(HI-6 and HGG-42),28% 45%reactiva-tions were observed by their 4-oxime isomers.In soman case the results were opposite. HI-6and HGG-42 showed remarkable reativation,but their 4-oxime isomers were ineffective.For sarin- and VX- phosphorylated AChE,alloximes showed high effctiveness.These re-sults indicated that there are conformationaldifferences among the active centre of theabove phosphorylated enzymes. The influ-ences of AChE allosteric agents showed thatC_(10) significantly increased the effects of TMB_4in sarin,soman and VX experiments,howev-er.it reduced the effect of TMB_4 significantlyin the tabun case. Propidium has no influenceon the reactivation of sarin,soman- and VX-phosphorylated AChE,but it significantly re-duced the effect of TMB_4 on reactivatingtabun-phosphorylated enzyme,These resultsconfirmed that the conformation in the activecentre of tabun-phosphorylated enzyme is ob-viously different from that of sarin-,soman-and VX-phosphorylated enzymes.