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RUI: Copper(I) Interactions With Zinc Finger Domains

RUI：铜 (I) 与锌指结构域的相互作用

基本信息

批准号：
1308675
负责人：
Kathryn Splan
金额：
$ 19万
依托单位：
Macalester College
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1308675&HistoricalAwards=false
关键词：
RUI Copper Interactions Zinc Finger

项目摘要

Through this award, the Chemistry of Life Processes Program is funding Professor Kathryn Splan from Macalester College to study the interaction of copper(I) with zinc finger protein domains. Cu(I) exhibits high affinity for thiolate ligands, which suggests that thiol-rich metalloprotein binding sites such as the ones present in zinc finger domains, may be disrupted at elevated copper concentrations. Professor Splan uses spectroscopic methods to measure the thermodynamic stability- and speciation of- copper-zinc finger peptide complexes. The research tests the ability of Cu(I) to affect the interactions between zinc fingers and DNA, and thus to modulate the function of zinc fingers. The results of this research may be relevant for understanding the mechanism of copper toxicity and homeostasis.The function of metalloproteins is linked to the metal ion(s) endogenous to the protein. Substitution of the endogenous metals with exogenous ones is likely to alter the structure and function of the protein. The research conducted by Professor Splan and undergraduate students at Macalaster College addresses such a substitution of zinc by copper in a zinc finger protein, which may underline the toxic effect of copper. In conducting this research, the students are trained in methods pertaining to both inorganic chemistry and biology. The research experiences provide the students with skills useful in many areas of chemical and biological research and prepare them for careers in STEM.

通过该奖项，生命过程化学项目正在资助马卡莱斯特学院的 Kathryn Splan 教授研究铜 (I) 与锌指蛋白结构域的相互作用。 Cu(I) 对硫醇盐配体表现出高亲和力，这表明富含硫醇的金属蛋白结合位点（例如锌指结构域中存在的结合位点）在铜浓度升高时可能会被破坏。 Splan 教授使用光谱方法测量铜-锌指肽复合物的热力学稳定性和形态。该研究测试了 Cu(I) 影响锌指和 DNA 之间相互作用的能力，从而调节锌指的功能。这项研究的结果可能有助于理解铜毒性和体内平衡的机制。金属蛋白的功能与蛋白质内源性的金属离子有关。用外源金属替代内源金属可能会改变蛋白质的结构和功能。斯普兰教授和麦卡拉斯特学院的本科生进行的研究解决了锌指蛋白中锌被铜取代的问题，这可能强调了铜的毒性作用。在进行这项研究时，学生们接受了无机化学和生物学相关方法的培训。研究经验为学生提供了在化学和生物研究许多领域有用的技能，并为他们在 STEM 领域的职业生涯做好准备。