What Controls Selenenic Acids? Understanding the Biochemistry of Selenocysteine

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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.