Structural Determinants of Leghemoglobin Reactivity

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HargroveMCB 0077890The long-range goal of this research is to develop a more comprehensive understanding of the structural and biophysical mechanisms, which regulate ligand binding to hemoglobins. The immediate goals are to use leghemoglobin as a complementary model system to test hypotheses for hemoglobin function, which are based heavily on the understanding of myoglobin. This work involves the use of site-directed mutagenesis, X-ray crystallography, and modern methods for the analysis of heme vibrational modes in combination with traditional kinetic and spectroscopic techniques to analyze the relationship of structure and function in soybean leghemoglobin. It has been demonstrated that this protein exploits different mechanisms for regulating ligand binding than those used by myoglobin. Therefore, a comprehensive study of leghemoglobin will undoubtedly provide new insight into hemoglobin structure and function. Heme proteins carry out a variety of important physiological functions. A basic understanding of monomeric heme proteins provides a starting point for investigating the structure and function of these different systems and allows for rational design to incorporate desired characteristics into better understood hemoglobins. It is not clear to what degree the current hypothesized mechanisms for hemoglobin regulation can be transferred to an understanding of other heme proteins. The research carried out through this project will test the current hypotheses for hemoglobin function using a comprehensive analysis of a monomeric hemoglobin, soybean leghemoglobin. A better understanding of ligand binding generated from a detailed study of this protein will complement our understanding of these processes gained from traditional model systems. The goals are to provide a more diverse and complete basis for exploring the same questions about more complex, multimeric hemoglobins, oxygen sensors, peroxidases, and related enzymes.