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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 核糖核苷酸还原酶（RNR）催化DNA复制所需的脱氧核糖核苷酸池的生产速率步骤。对于快速增殖的细胞至关重要，RNR是抗HSV和抗癌药物的成功靶标。尽管RNR2P+RNR4P异二聚体的晶体结构以及来自我们实验室的最近解决的RNR1P结构，但尚不清楚酵母RNR复合物组装的结构细节和RN1P的寡聚状态。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如何经历核苷酸依赖性寡聚。我们还将扩展这项工作，以研究人类RNR系统的DNTP依赖性寡聚化。在此提案中，我们将执行一系列小角度X射线散射实验，为高阶RNR复合物提供结构模型。