Thursday, November 21, 2024
11/21/2024
Enzymes using metal centers and/or organic radicals play many crucial roles in the fundamental biochemistry of human health, with deficiencies in their bioassembly or enzymatic functions associated with various diseases. The R. David Britt laboratory is using advanced spectroscopic techniques, such as multifrequency electron paramagnetic resonance (EPR), to understand the assembly and catalytic mechanism of a number of such metal and radical centers. Many important enzymes involved in multielectron oxidation or reduction reactions employ metal clusters in their catalysis. The Britt laboratory is studying how such clusters are assembled by identifying and interrogating assembly intermediates with their spectroscopic methods. For example, the [Fe-Fe] hydrogenase enzyme uses a complex multinuclear Fe-S “H-cluster”, containing organometallic Fe-CO and Fe-CN components, to catalyze reversible interconversion of H2 with protons and electrons. How does nature safely assemble such a center involving potentially dangerous CO and CN- species? Other experiments are unraveling the biosynthesis of the complex Fe-S “M-cluster” at the heart of the nitrogenase enzyme, which can incorporate Mo or V or an additional Fe in its active site. We are studying the biosynthesis of an interesting Cu(II) containing antibiotic, Fluopsin C. Radical S-adenosylmethione (rSAM) enzymes carry out many interesting reactions. In one interesting area, we are studying how they transform peptides into ribosomally-synthesized and post-translationally modified peptide (RiPP) products. Regulation of metal composition in cells is crucial, and we are examining a number of metal- binding proteins involved in metal ion sequestration and homeostasis, including a new project examining lanthanide binding in proteins such as lanmodulin. We are targeting a number of de novo designed proteins for detailed characterization, and we are starting new collaborations examining the reactivity of artificial metalloenzymes and DNAzymes. We continue to collaborate and provide advanced EPR support in a number of interesting metalloenzyme and radical enzyme arenas, including work to cryotrap, and characterize with high field EPR, the transient oxygen- generating S4 state of the photosystem II water oxidizing enzyme. And using site directed spin labeling as a tool, we are probing the dynamics of an all-protein biochemical oscillator that serves as nature’s simplest circadian clock.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
