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).

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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 DNA生物合成和修复、核糖核苷酸向脱氧核糖核苷酸的转化，以及 是抗癌治疗的重要靶点，人类 RNR 和其他 I 类 RNR 也是如此。 由两种类型的亚基组成，还原酶亚基，¿ ，以及自由基生成 ¿ .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复合物被研究过。 通过结构方法可视化，得到了大肠杆菌的对称对接模型。 基于亚基的各个晶体结构提出的复合物 此外，尽管 I 类 RNR 的活性复合物早已被证实。 认为存在为 ¿ 2¿2，I 类 RNR 的寡聚状态一直是 最近人们一直在努力了解 RNR 的寡聚状态。 由于酶的复杂性以及技术的局限性而受到阻碍 到目前为止，我们建议使用大肠杆菌和人类 RNR 的结构研究。 使用小角 X 射线散射 (SAXS)。