Structural Study of Sulfotransferases

工作概述：巯基转移酶代谢是一种类固醇激素等生物信号的失活过程，也是一种抵御环境毒物和致癌物质的防御系统。面对几乎无限数量的结构多样的化学物质，这些酶表现出广泛的底物特异性。因此，研究决定底物特异性的结构原理，以预测代谢及其对人类化学暴露敏感性的影响是很重要的。为了进行研究，我们使用了x射线晶体学和定点诱变。我们已经解决了雌激素、羟基萜类和苯酚磺酸转移酶的晶体结构。这些结构为了解硫转移酶催化的反应机理提供了新的思路。基于晶体结构的位点定向诱变定义了一个类似于结构的门，它决定了底物的特异性，也是所有细胞质硫转移酶的共同二聚体界面。巯基转移酶和糖基转移酶参与蛋白聚糖的糖胺基聚糖合成。我们解决了硫酸肝素n -去乙酰化酶/ n -硫转移酶和葡萄糖醛基转移酶1的晶体结构。

Summary of Work: Metabolism by sulfotransferases is an inactivation of biological signals such as steroid hormones and also a defense system against environmental toxicants and carcinogens. To encounter virtually unlimited numbers of structurally diverse chemiclas, these enzymes exhibit broad substrate specificity. Thus, it is important to investigate the structural principle determining the substrate specificity in order to predict the metabolisms and the resulted consequences to human susceptibililty to chemical exposure. For the investigation, we have used x-ray crystallography and site-directed mutagenesis. We have solved the crystal structure of estrogen, hydroxyteroid, and phenol sulfotransferases.These structures provided the insight into understanding the reaction mechanism catalyzed by sulfotransferase. Site-directed mutagenesis based on the crytal structres defined a stricture-like gate that determines substrate specificity and also the common dimer interface for all cytosolic sulfotransferase. Sulfotransferases and glycosyltransferases are involved in glycosaminylglycan synthesis of proteoglycans. We have solved the crystal structures of heparan sulfate N-deacetylase/N-sulfotrabsferase and glucuronosyltransferase 1.