What Controls Selenenic Acids? Understanding the Biochemistry of Selenocysteine

标题：是什么控制了亚硒酸？了解硒半胱氨酸的生物化学本项目研究含硒蛋白质的基本生物化学，以揭示使用硒而不是硫获得的独特优势，并最终使硒蛋白成为细胞生命的基本成分。在这些科学努力的过程中，残疾本科生将得到持续的培训。从大一开始，课题组将为学生提供意义深远的辅导和培训。此外，学生将通过广泛的网络获得支持，该网络源于我们为面临类似挑战的学生提供的REU计划，该计划旨在增加残疾学生对STEM学科的参与。将与STEM学生和专业人员广泛分享经验，以提高认识，并最终增加残疾人社区在我们社会的科学、社会和金融结构中的机会和参与。同样，社会也将受益于更多地接受这些少数群体和亚群，促进他们的思想、影响和专业知识的灌输。元素硒被并入稀有氨基酸硒半胱氨酸中，自然界利用它来扩大酶的化学多样性，使其超越20种典型氨基酸所具有的功能。由此产生的硒蛋白主要是参与细胞信号转导、解毒和维持氧化剂的酶。虽然人们普遍认为，在蛋白质中使用硒必须赋予蛋白质独特的性质和独特的优势，但将硒蛋白质区分开来的关键差异仍有待系统地研究和描述。本研究将重点研究硒半胱氨酸与氧化剂反应生成的反应中间体--亚硒酸。这些高活性的酸可以与附近的硫醇、胺、酰胺和氧化剂发生许多反应，这些反应将影响硒蛋白与自身和其他蛋白质的相互作用，并最终调节它们在信号级联中的功能。为了了解这种对生物功能的影响，将利用~(77)Se核磁共振波谱和质谱学来研究亚硒酸的寿命、它们被氧化剂进一步氧化的倾向以及它们与蛋白质伙伴的相互作用。这形成了一个研究计划，旨在阐明硒蛋白如何控制这种不寻常的半金属氨基酸--硒半胱氨酸，并利用其化学性质用于细胞。

TITLE: What Controls Selenenic Acids? Understanding the Biochemistry of SelenocysteineThis project studies the fundamental biochemistry of selenium containing proteins in order to uncover the unique advantages gained from employing selenium instead of sulfur and which ultimately make selenoproteins essential constituents of cellular life. During the course of these scientific efforts an undergraduate student with disabilities will be continuously trained. Starting in the freshmen year, the student will be provided with far-reaching mentoring and training by the research group. In addition, the student will receive support through an extensive network that originated from our accompanying REU program for students facing similar challenges and that is aimed at increasing participation of students with disabilities in the STEM disciplines. Experiences will be widely shared with both STEM students and professionals in order to raise awareness and to ultimately increase opportunities and participation of the disability community in the scientific, social and financial structure of our society. Likewise, society will benefit from increased acceptance of such minorities and subgroups, promoting infusion of their ideas, influences and expertise.The element selenium, incorporated into the rare amino acid selenocysteine, is used by nature to expand the chemical versatility of enzymes beyond what is available through the 20 canonical amino acids. The resulting selenoproteins are mostly enzymes that are involved in cellular signal transduction, detoxification, and maintenance of oxidants. While it is widely assumed that the use of selenium in proteins must impart unique properties and particular advantages, the key differences that set selenoproteins apart remain to be systematically studied and described. This research will focus on the reaction intermediate, selenenic acid, that is formed when selenocysteine reacts with oxidants. These highly reactive acids can undergo numerous reactions with nearby thiols, amines, amides and oxidants, which will affect selenoproteins interactions with itself and other proteins and ultimately modulate their function in signaling cascades. In order to understand this effect on biological function, 77Se NMR spectroscopy and mass spectrometry will be used to study the lifetimes of selenenic acid, their tendency to be further oxidized by oxidants and their interactions with protein partners. Together this forms a research plan that is designed to illuminate how selenoproteins control this unusual semi-metallic amino acid, selenocysteine, and harness its chemical properties for cellular use.