STRUCTURE-FUNCTION STUDIES OF YEAST RNR1

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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，该酶由a2和b2亚基的异聚物组成。a亚基（Rnr1）包含调控位点和催化位点；b亚基Rnr2包含对催化作用至关重要的异酪氨酸基。严格控制dNTP池对细胞活力至关重要；由于RNR在平衡dNTPs的相对水平方面起着至关重要的作用，它在转录上受到高度调节，通过细胞内各种亚基的区室化，在酿酒酵母中受到其蛋白抑制剂Sml1的调节。这些过程的分子基础尚不完全清楚。RNR对快速分裂的细胞至关重要，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