HOMOLOGY MODELLING & STRUCTURAL STUDIES OF MERCURIC ION REDUCTASE

汞还原酶是硫醇家族的一员。 氧化还原酶，其中包括谷胱甘肽还原酶 和硫酰胺脱氢酶。在我们对催化剂的研究中 汞还原酶的作用机制，它是一种经历 替代站点机制，一方面涉及到理解 在催化循环过程中发生的结构变化。最近，一位 芽孢杆菌的晶体结构RC607汞还原酶 至少以两种形式解决(使用和不使用NADP)。然而，大多数 在已经进行的生化研究中，重点是P. 铜绿假单胞菌Tn501汞还原酶。Tn501酶还没有 结晶了。RC607和Tn501汞还原酶40%相同 在它们的序列中。预计它们的结构高度 同源的。程序外观，可通过计算机图形学获得 实验室，使用两个序列的比对来生成一个 二聚体的同源模型。借助CGL的工作站和 程序，我们能够可视化可能的交互 在通过催化作用发展的不对称性中发挥作用 周而复始。从Tn501酶生成模型的比较 根据RC607酶的已知结构，我们将能够 将可能相关的相似之处和不同之处可视化 我们也从这些生物化学信息中获得了 酵素。我们想要开发一个催化循环的结构模型 并了解站间沟通的结构路径(S)。 从同源模型中获得的信息将使我们能够 构建活性位点通讯中断的突变酶。

Mercuric reductase is a member of the family of thiol oxidoreductases which, among others, includes glutathione reductase and lipoamide dehydrogenase. In our investigation of the catalytic mechanism of Mercuric Reductase, a homodimer that undergoes an alternate-site mechanism, one aspect involves understanding the structural changes that occur during the catalytic cycle. Recently, a crystal structure of the Bacillus sp. RC607 mercuric reductase was solved in at least two forms (with and without NADP). However, most of the biochemical studies that have been conducted focus on P. aeruginosa Tn501 mercuric reductase. The Tn501 enzyme has yet to be crystallized. RC607 and Tn501 mercuric reductases are 40% identical in their sequences. It is expected that their structures be highly homologous. The program LOOK, available through the Computer Graphics Laboratory, uses the alignment of the two sequences to ge nerate a homology model of the dimer. With the aid of CGL's workstations and programs, we were able to visualize possible interactions that may play a role in the asymmetry that develops through the catalytic cycle. From a comparison of the generated models of Tn501 enzyme against the known structure of the RC607 enzyme, we will be able to visualize similarities as well as differences that may be correlated with the biochemical information that we are also obtaining from these enzymes. We want to develop a structural model of the catalytic cycle and understand the structural pathway(s) of intersite communication. Information obtained from the homology models will allow us to construct mutant enzymes whose active site communication is disrupted.