DETERMINING ALLOSTERIC REGULATION OF RIBONUCLEOTIDE REDUCTASE

确定核糖核苷酸还原酶的变构调节

• 批准号: 8168655
• 负责人: Chris G Dealwis
• 金额: $ 0.27万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168655
• 关键词: Allosteric Regulation; Antineoplastic Agents; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA biosynthesis; Deoxyribonucleotides; Funding; Goals; Grant; Human; Institution; Nucleotides; Production; Proliferating; Research; Research Personnel; Resources; Ribonucleotide Reductase; Series; Source; Structural Models; Structure; System; United States National Institutes of Health; Work; Yeasts; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in production of the pool of deoxyribonucleotides necessary for DNA replication. Crucial for rapidly proliferating cells, RNR is a successful target for anti-HSV and anticancer drugs. Though there are crystal structures of the Rnr2p+Rnr4p heterodimer and the recently solved Rnr1p structure from our lab, the structural details of the assembly of the yeast RNR complex and the oligomerization state of Rn1p is not known. The overall goal of our experiments is to characterize interactions between Rnr1p and Rnr2p+Rnr4p complex, and to determine how Rnr1p undergo nucleotide dependent oligomerization. We will also extend this work to study the dNTP dependent oligomerization of the human RNR system. During this proposal we will perform a series of small-angle x-ray scattering experiments to provide a structural model for the higher-order RNR complex.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 核糖核苷酸还原酶 (RNR) 催化 DNA 复制所需的脱氧核糖核苷酸库生成过程中的限速步骤。 RNR 对于快速增殖的细胞至关重要，是抗 HSV 和抗癌药物的成功靶点。虽然我们实验室有Rnr2p+Rnr4p异二聚体的晶体结构和最近解析的Rnr1p结构，但酵母RNR复合物组装和Rn1p寡聚状态的结构细节尚不清楚。我们实验的总体目标是表征 Rnr1p 和 Rnr2p+Rnr4p 复合物之间的相互作用，并确定 Rnr1p 如何进行核苷酸依赖性寡聚化。我们还将扩展这项工作来研究人类 RNR 系统的 dNTP 依赖性寡聚化。在这个提案中，我们将进行一系列小角度 X 射线散射实验，为高阶 RNR 复合体提供结构模型。