STRUCTURE-FUNCTION STUDIES OF YEAST RNR1

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。核糖核苷酸还原酶(RNR)催化DNA从头合成的限速步骤，并受dNTPs的相对水平的变构控制，以维持细胞内脱氧核苷酸三磷酸(DNTPs)的平衡。在真核生物中，该酶包括a2和b2亚基的异位寡聚体。A亚基(Rnr1)含有调节和催化位点；b亚基Rnr2含有对催化至关重要的二铁酪氨酸自由基。对dNTP池的严格控制对细胞活力至关重要；由于RNR在平衡dNTP的相对水平方面起着至关重要的作用，它在转录上、变构上受到高度调控，在细胞内的各个亚基的区划中，在酿酒酵母中受到其蛋白抑制剂Sml1的高度调控。这些过程的分子基础还没有完全被理解。RNR对细胞的快速分裂至关重要，是癌症治疗的靶点

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 de novo DNA synthesis and is allosterically controlled by relative levels of dNTPs to maintain a balanced pool of deoxynucleotide triphosphates (dNTPs) in the cell. In eukaryotes, the enzyme comprises a hetero-oligomer of a2 and b2 subunits. The a subunit (Rnr1) contains regulatory and catalytic sites; Rnr2, the b subunit, houses the diferric-tyrosyl radical crucial for catalysis. Tight control of dNTP pools is vital for cell viability; due to the crucial role RNR plays in balancing the relative levels of dNTPs, it is highly regulated transcriptionally, allosterically, by compartmentalization of the various subunits within the cell, and in S. cerevisiae by its protein inhibitor Sml1. The molecular basis for these processes is not fully understood. Crucial for rapidly dividing cells, RNR is a target for cancer therapy