LONG RANGE RADICAL INITIATION IN E COLI RIBONUCLEOTIDE REDUCTASE

大肠杆菌核糖核苷酸还原酶中的长程自由基引发

• 批准号: 7723929
• 负责人: JOANNE STUBBE
• 金额: $ 0.1万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723929
• 关键词: Binding; Binding Sites; Catalysis; Complex; Computer Retrieval of Information on Scientific Projects Database; Cysteine; Diphosphates; Docking; Electron Transport; Funding; Grant; Housing; Institution; Iron; Measurement; Modeling; Nucleotides; Pathway interactions; Process; Proteins; Range; Rate; Research; Research Personnel; Resources; Ribonucleotide Reductase; Source; Structure; Substrate Specificity; Thinking; United States National Institutes of Health; cofactor; nucleoside diphosphate

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. E.coli ribonucleotide reductase catalyzes the conversion of nucleoside diphosphates (NDP) to deoxynucleoside diphosphates. The active protein is composed of two homodimeric subunits (R1 and R2) thought to form a 1:1 complex. R1 binds the NDP substrates, houses the essential cysteines required for catalysis and the binding sites for the allosteric effectors that govern substrate specificity and turnover rates. R2 harbors the essential di-iron tyrosyl radical cofactor on residue 122 (Y?). A major unresolved issue is the mechanism of radical initiation: how the tyrosyl radical (Y?) in R2 generates a transient thiyl radical (C439?) in R1 required for nucleotide reduction. The current model for the radical initiation process involves a specific electron transfer pathway, which traverses a distance of 3.5 nm, derived from a docking model of the R1 and R2 structures, but a substantial part of the pathway is not apparent from the available structural information. A measurement of the distance between Y122 and C439 was imperative to establish the radical initiation model.

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。子项目和 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。 大肠杆菌核糖核苷酸还原酶催化核苷二磷酸（NDP）转化为脱氧核苷二磷酸。活性蛋白由两个同源二聚体亚基（R1和R2）组成，被认为形成1：1复合物。R1结合NDP底物，容纳催化所需的必需半胱氨酸和控制底物特异性和周转率的变构效应物的结合位点。R2在残基122（Y？）上含有必需的二铁酪氨酰自由基辅因子。一个尚未解决的主要问题是自由基引发的机制：酪氨酰基自由基（Y？）在R2中产生一个瞬时的硫基自由基（C439？）在R1中需要核苷酸减少。自由基引发过程的当前模型涉及特定的电子转移途径，其穿过3.5 nm的距离，来自R1和R2结构的对接模型，但该途径的实质部分从可用的结构信息中不明显。测量Y122和C439之间的距离是建立自由基引发模型的必要条件。