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.

通过此奖项，化学生命过程的化学过程计划正在为加尔文学院的戴维·本森（David Benson）博士提供资金，以调查如何以及为什么某些蛋白质成为抗氧化剂。抗氧化剂在各种营养上有价值的食物中是氧化而不是细胞成分（例如蛋白质，膜或DNA）的小分子。一类新的抗氧化剂 - 蛋白质修饰以含有抗氧化剂，同时仍附着在蛋白质上，从而增加了修饰蛋白的氧化。实验程序将通过使用多种生化，紫外吸光度，荧光和质谱检测方法来详细介绍这些蛋白质修饰如何在最小化自身或其他蛋白质中最小化氧的氧气中形成和功能。这项工作将在培训本科生，加尔文学院和大急流城社区学院进行培训时，如何进行研究，以准备在高技能的技术劳动力中工作。这项工作的发现将有助于更好地理解生物系统的韧性，同时还准备下一代科学劳动力。这项工作将集中于酪氨酸后翻译后修饰，这些修饰可以在生理条件下可逆地氧化。这些改良的酪氨酸最著名的是参与氧化还原催化。 The role of one modified tyrosine, 3'-(S-cysteinyl)-tyrosine (Cys-Tyr), will be studiod in aerotolerance of a gut bacteria (Bacteroides fragilis), minimizing protein oxidation of a protein that regulates cellular cysteine ​​concentrations (rat cysteine ​​dioxygenase), and potentially modulating ubiquitination of proteins.最近开发的荧光测定法将用于在多种条件下快速确定CYS-TYR反应产量，并将蛋白质功能的变化与Cys-Tyr的形成相关。由于CYS-TYR表现出可逆的氧化化学和其他改良的酪氨酸，因此假设是可以确定Cys-TYR的抗氧化作用。这种作用将很重要，因为共价连接将抗氧化功能定位在蛋白质上，并为响应氧化物胁迫提供了一种新的蛋白质功能。

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.