DETERMINING ALLOSTERIC REGULATION OF RIBONUCLEOTIDE REDUCTASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 核糖核苷酸还原酶（RNR）催化DNA复制所必需的脱氧核糖核苷酸池的产生中的限速步骤。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。虽然有Rnr 2 p + Rnr 4p异二聚体的晶体结构和我们实验室最近解决的Rnr 1 p结构，但酵母RNR复合物组装的结构细节和Rn 1 p的寡聚化状态尚不清楚。我们的实验的总体目标是表征Rnr 1 p和Rnr 2 p + Rnr 4p复合物之间的相互作用，并确定Rnr 1 p如何进行核苷酸依赖性寡聚化。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。在这个建议中，我们将进行一系列的小角度X射线散射实验，提供一个结构模型的高阶RNR复杂。

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.