With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Aimin Liu from The University of Texas at San Antonio to investigate the structure and mechanism of two human enzymes involved in the oxidative sulfur metabolism. The two enzymes of interest, cysteine dioxygenase and cysteamine dioxygenase, are responsible for activating oxygen to process organic thiol moieties. The activity of these two enzymes is essential to manage metabolic cysteine and taurine concentrations and it is associated with autoimmune and neurological conditions, cellular signaling, energy balance, and fat metabolism. Integrated training is incorporated in the research project, which provides to students comprehensive and hands-on learning opportunities in biochemical and structural biology techniques. A multimedia presentation on electron paramagnetic resonance spectroscopy will be created and used to provide to students a tangible demonstration of how this advanced spectroscopy can clarify chemical properties of critical biomolecular systems.
This research project seeks to reveal the mechanistic implications of adding oxygen atoms to electron-rich sulfur as well as the nature of the catalytic contribution of a protein-derived cofactor. The thiol dioxygenases utilize a mononuclear ferrous center to facilitate the incorporation of molecular oxygen into the thiol moiety of their respective substrates. These enzymes stand out as unique among dioxygenases because they add two of the oxygen atoms of molecular oxygen to a single substrate atom. Though other dioxygenases have been well studied, thiol dioxygenation is expected to proceed via a distinct mechanism that has not been well established yet. Dr. Liu is investigating the formation of the catalytic ensemble of these enzymes, namely an iron- and oxygen-dependent process for generating a catalytic amplifier known as the protein-derived cofactor. A wide array of techniques, including protein engineering, EPR spectroscopy, stopped-flow rapid kinetics, and protein X-ray crystallography, are employed in the determination of the chemical steps of cofactor biogenesis and sulfur oxygenation. The completion of this project is expected to reveal new mechanistic implications of adding two oxygen atoms to one electron-rich sulfur as well as the nature of the catalytic contribution of the protein-derived cofactor to sulfur metabolism.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.