Regulation and Structure of the mer Operon

mer操纵子的调控和结构

• 批准号: 9218636
• 负责人: Anne Summers
• 金额: $ 28.5万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9218636&HistoricalAwards=false
• 关键词: Regulation; Structure; mer; Operon

Metal ions figure significantly in the activity of many enzymes biological systems also make very subtle distinctions among metallic elements to control fundamental information transduction processes. Moreover, proteins with active-site sulfhydryl groups (potential metal binding targets) play key roles in DNA replication and repair. Presently, our understanding of what determines specific protein-metal interactions and of how alternative metals can modulate protein behavior is incomplete. Summers studies the bacterial mercury (Hg) resistance (mer) locus, an operon controlled by a small, Hg-responsive, DNA binding, transcriptional activator/repressor, MerR. Her work has focussed on MerR interactions with its cognate DNA site, merOP, and with RNA polymerase. She will use molecular genetics and biochemistry to discern the MerR domains which enable it to sequester RNA polymerase at merOP prior to induction and those responsible for the DNA distortion which takes place during activation. She will dissect the relationship between the mer operon and the chromosomally encoded oxidative shock regulon. Finally, she will employ random and site specific mutagenesis to obtain MerR mutants responsive to transition metals other than Hg(II). These variant MerR proteins will be examined in vitro for their metal and DNA binding properties. %%% Certain micro-organisms have the ability to grow in the presence of chemicals which are toxic to most other organisms. One way this is accomplished is through conversion of the toxic form of the chemical to a non or less toxic form. This proposal investigates the genetic mechanisms which regulate and control the expression of a set of genes in bacteria which function in the detoxification of mercury. $$$//

金属离子在许多酶的活性中发挥着重要作用，生物系统也在金属元素之间做出非常微妙的区别，以控制基本的信息转导过程。 此外，具有活性位点巯基（潜在金属结合靶标）的蛋白质在 DNA 复制和修复中发挥着关键作用。 目前，我们对决定特定蛋白质-金属相互作用的因素以及替代金属如何调节蛋白质行为的理解还不完整。 Summers 研究细菌汞 (Hg) 抗性 (mer) 位点，这是一种由小型 Hg 响应性 DNA 结合转录激活子/阻遏子 MerR 控制的操纵子。 她的工作重点是 MerR 与其同源 DNA 位点 merOP 以及 RNA 聚合酶的相互作用。 她将利用分子遗传学和生物化学来辨别 MerR 结构域，这些结构域使其能够在诱导前将 RNA 聚合酶隔离在 merOP 上，以及那些负责激活过程中发生的 DNA 扭曲的结构域。 她将剖析 mer 操纵子和染色体编码的氧化休克调节子之间的关系。 最后，她将采用随机和位点特异性诱变来获得对 Hg(II) 以外的过渡金属有反应的 MerR 突变体。 这些变体 MerR 蛋白将在体外检查其金属和 DNA 结合特性。 %%% 某些微生物能够在对大多数其他生物体有毒的化学物质存在下生长。 实现这一点的一种方法是将化学物质的有毒形式转化为无毒或毒性较小的形式。 该提案研究了调节和控制细菌中一组基因表达的遗传机制，这些基因在汞解毒中发挥作用。 $$$//