EPSP合成酶的特性及新抑制剂的研究进展

Development on Property of EPSP Synthase and Its New Inhibitors

概述了 EPSP合成酶的生理作用。高等植物前体 EPSP合成酶进入叶绿体后 ,经剪切而成成熟 EPSP合成酶并定位于叶绿体内质膜上 ;EPSP合成酶的三维结构上存在三个活性区域 ,改变活性区域的氨基酸残基可对草甘膦产生抗性 ,同时表明了酶与草甘膦的结合位点 ;不同生物的 EPSP合成酶有高的同源性。 EPSP合成酶催化底物反应机理为 :PEP首先与酶形成过渡态 ,而后和 S3P形成缩酮四面体 ,最后生成 EPSP。草甘膦与 EPSP合成酶、EPSP形成三元复合物而阻断了 EPSP合成酶的催化作用 ;以 EPSP和 S3P· glyphosate为分子模型 ,设计合成的化合物对 EPSP合成酶的活性有抑制作用。

Physiology of EPSP synthase was briefly reviewed.The enzyme is a chloroplast localized enzyme of the shikimate pathway in plants.Cytosolic precursor,the pre EPSP synthase,becomes mature EPSP synthase after a cut process of the amino terminal transit peptide of cytosolic precursor in the chloroplast.There are three activity domains in 3D structure of EPSP synthase,and single amino acid replacement in the three domains could confer glyphosate tolerance.It was identified there are glyphosate binding sites in the three domains.EPSP sythases in various species are significantly similar.Mechanism of the reaction catalyzed by EPSP synthase is as follows:enzyme bound PEP becomes intermediate enzyme PEP,then combines with S3P to form enzyme bound ketal,then produce EPSP.Glyphosate,as a transition state inhibitor of EPSP synthase,inhibit the canalization of the enzyme as an EPSP synthase·EPSP·glyphosate ternary complex.Intermediate mimic inhibitors from EPSP derivative and S3P·glyphosate can inhibit EPSP synthase activity.