Heme Protein Structure and Dynamics

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DESCRIPTION (provided by applicant): Structural and functional studies will be carried out in order to provide a molecular level understanding of the role of heme proteins in fundamental physiological processes, including respiration, metabolism, and the regulation of cellular responses. Special emphasis will be placed on the new class of heme sensor proteins. The signal transducers guanylate cyclase and CooA, and the heme-regulated enzyme cystathionine beta synthase, have been selected for detailed characterization and dynamical studies of protein conformational change. In addition, the determinants of metal ion insertion into heme will be studied by comparing the enzyme ferrochelatase with a set of catalytic antibodies that carry out the same reaction. Resonance Raman spectroscopy will be applied as a structural monitor of the heme group, and of its interaction with the surrounding protein and with exogenous ligands. Dynamical studies will utilize pulse-probe time-resolved resonance Raman spectroscopy on picosecond and longer time scales. Ab initio computation with current DFT techniques will be employed to extract maximum information from the spectra, and to provide insight into the molecular mechanisms of the heme-protein interactions.