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).

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 核糖核苷酸还原酶（RNR）使用基于自由基的化学来催化必不可少的步骤 在DNA的生物合成和修复中，核糖核苷酸转化为脱氧核糖核苷酸和 是抗癌治疗的重要靶标。人类RNR和其他I级RNR是 由两种类型的亚基组成，即还原亚基和自由基生成。 大肠杆菌RNR已被广泛研究，并用作I类RNR的模型系统。 尽管它对癌症研究的重要性，但没有完整的I类RNR的复合体 通过结构方法可视化。结果，大肠杆菌的对称对准模型 基于亚基的单个晶体结构已提出的复合物 未经验证。而且，尽管长期以来，I级RNR的活跃综合体 被认为存在为„2¿2，I级RNR的寡聚状态一直是 最近的一些辩论。理解RNR的寡聚状态的努力已经 受酶的复杂性以及具有限制的技术的限制 到目前为止，我们已经使用了。在这里，我们建议使用大肠杆菌和人类RNR的结构研究 使用小角度X射线散射（SAXS）。