SOLUTION SAXS STUDIES OF SUBUNIT INTERACTIONS IN RIBONUCLEOTIDE REDUCTASE

核糖核苷酸还原酶中亚基相互作用的解决方案 SAXS 研究

• 批准号: 8363533
• 负责人: CATHERINE L DRENNAN
• 金额: $ 2.28万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363533
• 关键词: Biological Models; Chemistry; Complex; DNA Repair; DNA biosynthesis; Deoxyribonucleotides; Docking; Enzymes; Escherichia coli; Funding; Grant; Human; Individual; Methods; Modeling; National Center for Research Resources; Oxidoreductase; Principal Investigator; Research; Research Infrastructure; Resources; Ribonucleotide Reductase; Ribonucleotides; Roentgen Rays; Solutions; Source; Structure; Techniques; United States National Institutes of Health; anticancer research; base; cancer therapy; cost

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Ribonucleotide reductases (RNRs) use radical-based chemistry to catalyze an essential step in DNA biosynthesis and repair, the conversion of ribonucleotides to deoxyribonucleotides, and are important targets for anti-cancer therapy. Human RNR and other class I RNRs are composed of two types of subunits, the reductase subunit, ¿, and the radical-generating ¿. E. coli RNR has been extensively studied and serves as a model system for class I RNRs. Despite its importance for cancer research, no intact complex of class I RNRs has ever been visualized by structural methods. As a result, a symmetrical docking model for the E. coli complex that has been proposed based on the individual crystal structures of the subunits has not been verified. Moreover, although the active complex of class I RNRs has long been thought to exist as ¿2¿2, the oligomerization state of class I RNRs has been the subject of some recent debate. Efforts to understand the oligomerization states of RNR have been hindered by the complexity of the enzyme as well as by the limitations in techniques that have been used thus far. Here, we propose to use a structural study of E. coli and human RNRs using small-angle X-ray scattering (SAXS).

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 核糖核苷酸还原酶（RNR）使用基于自由基的化学来催化一个重要步骤 在DNA生物合成和修复中，核糖核苷酸转化为脱氧核糖核苷酸， 是抗癌治疗的重要靶点。人类RNR和其他I类RNR是 由两种亚基组成还原酶亚基和自由基生成亚基。E. 大肠杆菌RNR已被广泛研究，并作为I类RNR的模型系统。 尽管I类RNR对癌症研究很重要，但迄今为止还没有完整的I类RNR复合物被用于癌症研究。 通过结构化方法可视化。最后，建立了E.杆菌 基于亚基的单个晶体结构提出的复合物具有 没有被证实。此外，尽管I类RNR的活性复合物长期以来一直是 被认为以<$2 <$2存在，I类RNR的寡聚化状态一直是研究的主题。 最近的一些辩论。理解RNR的寡聚化状态的努力已经被证明是可行的。 由于酶的复杂性以及技术的局限性， 到目前为止一直在使用。在这里，我们建议使用的结构研究E。大肠杆菌和人RNR 使用小角X射线散射（SAXS）。