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1251 Wescoe Hall Drive Malott Hall, Room 4025 University of Kansas Lawrence, KS 66045 Phone: (785) 864-2901 Fax: (785) 864-5396 Email: mmure@ku.edu |
Bioanalytical and Bioinorganic Chemistry
Understanding the chemistry and biological functions of enzymes.
Quinones are highly reactive in solution and are used as catalysts and electron-transfer mediators. However, this reactivity also means that some are very toxic. Nature has found ways to control and take advantage of the chemical potential of quinones by encapsulating them inside of proteins to provide the optimal environment for catalysis. There is a family of enzymes that contain quinones as their organic cofactors that catalyze the oxidation of biogenic amines, alcohols and sugars. These enzymes are called quinoproteins and they are ubiquitous. Humans have at least two types of quinoproteins that are crucial for cellular integrity and development, biological signal transduction, neurotransmitter metabolism, and connective tissue formation. Aberrant expression levels of these proteins are linked to health problems and diseases such as cancer, fibrosis and diabetes. We are interested in understanding the mechanism of these enzymes at the chemistry/biology interface. A combination of techniques (organic synthesis, biochemistry, spectroscopy, electrochemistry, molecular cell biology, developmental biology) will be applied. An understanding the mechanism will lead to the development of specific inhibitors that will have a high chance of producing therapeutic agents.
Recent publications:
Moore, R.H., Spies, M.A., Culpepper, M.B., Murakawa, T., Hirota, S., Okajima, T., Tanizawa, K. and Mure, M. "Trapping of a Dopaquinone Intermediate in the TPQ Cofactor Biogenesis in a Copper Amine Oxidase from Arthrobacter globiformis" J. Am. Chem. Soc. 2007, 129, 11524-11534.
Knowles, P., Kurtis, C., Murray, J., Saysell, C., Tambyrajah, W., Wilmot, C., McPherson, M., Phillips, S., Dooley, M., Brown, D., Rogers, M., and Mure, M. "Hydrazine and amphetamine binding to amine oxidases: old drugs with new prospects" J. Neural. Transm. 2007, 114, 743-746.
Mure, M., Brown, D. E., Saysell, C., Kurtis, C. R., Rogers, M., Wilmot, C. M., Phillips, S. E. V., McPherson, M. J., Knowles, P. F. and Dooley, D. M. "Role of the Interactions between the Active Site Base and the Substrate Schiff Base in Amine Oxidase Catalysis. Evidence from Structural and Spectroscopic Studies of the 2-Hydrazinopyridine Adduct of E.coli Amine Oxidase" Biochemistry 2005, 44, 1568-1582.
Mure, M., Kurtis, C. R., Brown, D. E., Rogers, M., Wilmot, C. M., Parsons, M., Phillips, S. E. V., McPherson, M. J., Knowles, P. F. and Dooley, D. M. “Active Site Rearrangement of the 2-Hydrazinopyridine Adduct in E.coli Amine Oxidase to an Azo Cu(II) Chelate form: A Key Role for Y369 in Controlling the Mobility of the TPQ-2HP Adduct" Biochemistry 2005, 44, 1583-1594.
Limburg, J., Mure, M. and Klinman, J. P. "Cloning and Characterization of Histamine Dehydrogenase from Nocardioides simplex" Arch. Biochem. Biophy. 2005, 436, 8-22.
Matsunami, H., Okajima, T., Hirota, S., Yamaguchi, H., Hori, H., Mure, M., Kuroda, S. and Tanizawa, K. "Chemical Rescue of a Site-specific Mutant of Bacterial Copper Amine Oxidases for Generation of the Topa Quinone Cofactor" Biochemistry 2004, 43, 2178-2187.
Mure, M. "Tyrosine-derived Quinone Cofactors" Acc. Chem. Res. 2004, 37, 131-139.
