Research Interests: Bioinorganic Chemistry, Allostery in Gas Sensing Metalloproteins, Metallosensor design
Our group studies gas-sensing metalloproteins, specifically how the interaction of a gas molecule with a metal center alters protein structure and function. Metalloproteins serve as sensors and signal transducers in a number of important biological processes. For example, NO regulates your blood pressure by interacting with heme containing soluble guanylyl cyclase. Bacteria use metalloproteins to sense gases such as O2, CO, and NO in their environment, and plants use copper to detect ethylene, a hormone that regulates plant development.
In our laboratory, research efforts are directed towards understanding how gas sensing occurs at a metal center, and how changes in the coordination chemistry at the metal center are coupled to allosteric conformational changes in the protein. Through our studies of the mammalian NO-sensor soluble guanylyl cyclase and the bacterial CO-sensor CooA, we learned that interaction of gas molecules with the heme centers induces changes in the coordination geometry, and these changes correlate with functional changes in the proteins. Our current work aims to elucidate the mechanisms by which the coordination changes are communicated through the protein, resulting in global structural changes. To this end we study several bacterial gas-responsive transcription factors and newly discovered types of heme-containing gas sensor that regualte circadian rhythm in higher organisms.
Another project investigates the role of heme in the enzyme cystathionine-b-synthase (CBS). CBS is a critical enzyme that regulates sulfur amino acid metabolism, and this protein is the site of disease-causing mutations. We study the effect of these mutations on the biochemistry of the enzyme as a tool to understand how this unusual enzyme uses its heme.
In our studies we utilize a variety of biochemical and biophysical methods, including enzyme kinetics, protein modification or mutagenesis, mass spectrometry, electronic absorption, EPR, resonance Raman, CD and fluorescence spectroscopies, to probe the structure-function relationships. Our group is interactive and interdisciplinary, with active collaborations at UW and other institutions.