RUI: Protein Tyrosine Oxidations to Maintain Cellular Redox State

RUI：蛋白质酪氨酸氧化维持细胞氧化还原状态

• 批准号: 1709787
• 负责人: David Benson
• 金额: $ 24.9万
• 依托单位: Calvin University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709787&HistoricalAwards=false
• 关键词: RUI; Protein; Tyrosine; Oxidations; Maintain

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. David Benson from Calvin College to investigate how and why some proteins become antioxidants. Antioxidants, in a variety of nutritionally valuable foods, are small molecules that get oxidized rather than cellular components such as proteins, membranes, or DNA. A new class of antioxidants-proteins modified to contain antioxidants while still being attached to the protein-dramatically decreases the oxidation of the modified protein. The experimental procedures will detail how these protein modifications form and function in minimizing oxygen addition to themselves or other proteins by using a variety of biochemical, ultraviolet absorbance, fluorescence, and mass spectrometric detection methods. This work will be performed while training undergraduates, at Calvin College and Grand Rapids Community College, on how to perform research in preparation for working in a highly skilled technical workforce. The findings of this work will contribute to better understanding the resilience of biological systems while also preparing the next generation of the scientific workforce.This work will focus on tyrosine post-translational modifications that can be reversibly oxidized under physiological conditions. These modified tyrosines are best known to participate in redox catalysis. The role of one modified tyrosine, 3'-(S-cysteinyl)-tyrosine (Cys-Tyr), will be studied in aerotolerance of a gut bacterium (Bacteroides fragilis), minimizing protein oxidation of a protein that regulates cellular cysteine concentrations (rat cysteine dioxyngease), and potentially modulating ubiquitination of proteins. A recently developed fluorescence assay will be used to rapidly determine Cys-Tyr reaction yield under a variety of conditions and correlate changes in protein function with Cys-Tyr formation. Due to the reversible oxidation chemistry displayed by Cys-Tyr, and other modified tyrosines, the hypothesis is that an anti-oxidant role for Cys-Tyr may be established. This role would be important as covalent-attachment localizes anti-oxidant function to a protein and provides a new protein function in response to oxidative stress.

凭借该奖项，化学系的生命过程化学项目正在资助卡尔文学院的 David Benson 博士研究一些蛋白质如何以及为何成为抗氧化剂，在各种具有营养价值的食物中，抗氧化剂是被氧化而不是被氧化的小分子。与蛋白质、细胞膜或 DNA 等细胞成分相比，一类新的抗氧化剂——经过修饰的蛋白质含有抗氧化剂，同时仍附着在蛋白质上——可显着减少细胞的氧化。实验程序将详细说明这些蛋白质修饰如何形成和发挥作用，通过使用各种生化、紫外吸光度、荧光和质谱检测方法来最大限度地减少自身或其他蛋白质的氧添加。这项工作将在培训本科生时进行。 ，在卡尔文学院和大急流城社区学院，研究如何进行研究，为在高技能技术劳动力中工作做好准备。这项工作的结果将有助于更好地了解生物系统的弹性，同时也为下一代科学工作者做好准备。这项工作将重点关注酪氨酸翻译后修饰可以在生理条件下可逆地氧化，这些修饰的酪氨酸最著名的是参与氧化还原催化的一种修饰的酪氨酸，3'-(S-半胱氨酰)-酪氨酸(Cys-Tyr)。研究肠道细菌（脆弱拟杆菌）的空气耐受性，最大限度地减少调节细胞的蛋白质的蛋白质氧化半胱氨酸浓度（大鼠半胱氨酸双加氧酶），以及可能调节蛋白质的泛素化，最近开发的荧光测定将用于快速确定各种条件下的 Cys-Tyr 反应产量，并将蛋白质功能的变化与 Cys-Tyr 相关联。由于 Cys-Tyr 和其他修饰的酪氨酸表现出可逆氧化化学，因此假设 Cys-Tyr 具有抗氧化作用，该作用可能很重要。共价连接将抗氧化功能定位于蛋白质，并提供新的蛋白质功能以应对氧化应激。

项目成果

Protein oxidation involved in Cys-Tyr post-translational modification

• DOI: 10.1016/j.jinorgbio.2017.08.028
• 发表时间: 2017-11-01
• 期刊: JOURNAL OF INORGANIC BIOCHEMISTRY
• 影响因子: 3.9
• 作者: Hromada, Susan E.;Hilbrands, Adam M.;Benson, David E.
• 通讯作者: Benson, David E.