个人简介

Dr. Hille completed his undergraduate work in Chemistry at Texas Tech University, graduating with honors in 1974. He received his Ph.D. in Biochemistry from Rice University in 1979, working with John S. Olson. After postdoctoral work with Vincent Massey at the University of Michigan, he took a faculty position in the Department of Molecular and Cellular Biochemistry at the Ohio State University in 1985, where he became a Full Professor in 1995. He moved to UC Riverside in 2007 as a Chancellor’s Professor, and is presently a Distinguished Professor of Biochemistry.

研究领域

My research program focuses the reaction mechanisms of oxidoreductase enzymes - particularly those possessing molybdenum or flavin in their active sites - and biological electron transfer. The molybdenum-containing enzymes catalyze the incorporation of oxygen into a variety of organic and inorganic compounds, and constitute an important enzyme class within the oxidoreductases. These enzymes have been only poorly understood in comparison to other biological systems that contain heme, flavin, non-heme iron or copper. Working with representative members of each of the three major families of molybdenum enzymes, we have successfully identified the fundamental aspects of the catalytic sequences of these enzymes, and in each case established the overall chemical course of the reaction. Particularly in the case of the molybdenum hydroxylase family (as represented by xanthine oxidase), work in our laboratory has elucidated the overall reaction mechanism, characterizing each of the principal intermediates in the course of the reaction both spectroscopically and crystallographically. Current work focuses on two ancient yet poorly understood enzymes, formate dehydrogenase and CO dehydrogenase.

Enzymology Physical Biochemistry Molecular Biophysics

近期论文

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Niks, D, Duvvuru, J., Escalona, M. & Hille, R. (2016) Spectrosccopic and kinetic characterization of the soluble, NAD+-dependent formate dehydrogenase from Ralstonia eutropha, J. Biol. Chem. 291, 1162-1174. Wang, J., Krizowski, S., Fischer, K, Niks, D., Tejero, J., Wang, L., Sparacino-Watkins, C., Ragireddy, P., Frizzell, S., Kelley, E., Shiva, S., Zhang, Y., Hille, R., Basu, P., Schwarz, G., Gladwin, M.T. (2015) Sulfite oxidase catalyzes single electron transfer reaction at its molybdenum domain to reduce nitrite to NO. Antiox. Redox. Sign. 23, 283-294. Lee, M.-C., Velayutham, M., Shoji, H., Yoshino, F., Hille, R., & Zweier, J.L. (2014) Measurement and characterization of superoxide generation from xanthine dehydrogenase: A redox regulated pathway of radical generation in ischemic tissues. Biochemistry 53, 6615-6623. Hall, J., Reschke, S., Cao, H., Leimkühler, S. & Hille, R. (2014) The reaction mechanism of xanthine dehydrogenase from R. capsulatus. J. Biol. Chem. 289, 32121-32130. Cao, H., Pauff, J.M., & Hille, R. (2014) X-ray crystal structure of xanthine oxidase in complex with flavonoid inhibitor quercitin. J. Nat. Prod. 77, 1693-1699 Anderson, R.F., Shinde, S.S, Hille, R, Rothery, R.A., Weiner, J.H., Rajagukguk, S., Maklashina, E. & Cecchini, G. (2014) Efficient Electron Transfer to the Heme in Complex II Involves the [3Fe-4S] and Quinone Sites of the Enzyme. Biochemistry 53, 1637-1646. Cao, H., Hall, J., & Hille, R. (2014) Crystal structures of xanthine oxidoreductase complexed with guanine and indole-3-aldehyde. Biochemistry, 533-541. Hille, R., Hall, J., & Basu, P. The mononuclear molybdenum enzymes. (2014) Chem. Rev. 114, 3963-4038. Hille, R. Molybdenum-containing iron-sulfur proteins. (2014) In Iron-Sulfur Clusters in Chemistry and Biology (T.A. Roualt, ed.) Walter de Gruyter, Berlin, pp. 133-210. Pushie, M.J., Cotelesage, J.J.H., Lyashenko, G., Hille, R. & George, G.N. (2013) X-ray absorption spectroscopy of a quantitatively Mo(V) dimethyl sulfoxide reductase species. Inorg. Chem. 52, 2830-2837. Shanmugam, M., Wilcoxen, J., Habel-Rodriguez, D., Kirk, M.L., Hoffman, B.M. & Hille, R. (2013) 13C and 63,65Cu ENDOR studies of CO dehydrogenase from Oligotropha carboxidovorans. Experimental evidence in support of a copper-carbonyl intermediate. J. Am. Chem. Soc. 135, 17775-17782. Reschke, S., Niks, D., Wilson, H., Sigfridsson, K.G.V., Haumann, M., Rajagopalan, K.V., Hille, R. & Leimkühler, S. (2013) Impact of the cysteine molybdenum ligand by selenocysteine on structure and function of the active site in human sulfite oxidase. Biochemistry 52, 8295-8303. Wilcoxen, J., & Hille, R. (2013) The hydrogenase activity of CO dehydrogenase from Oligotropha carboxidovorans. J. Biol. Chem. 288, 36052-36060. Appel, A.M., Bercaw, J.E., Bocarsly, A..B., Dobbek, H., Dubuis, M., Dubois, D., Ferry, J.G., Fujita, E., Hille, R., Kenis, P.J.A., Kerfeld, C.A., Morris, R.H., Peden, C.H.F., Portis, A.R., Ragsdale, S.J., Rauchfuss, T.B., Reek, J.N.H., Seefeldt, L., Thauer, R.K., & Waldrop, G.L. (2013) Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO2 Fixation. Chem. Rev. 113, 6621-6658. Hille, R. (2013) The assimilatory nitrate reductases. In Handbook of Flavoproteins, vol 2 (R. Hille, S.M. Miller and B. Palfey, eds), Walter de Gruyter, Berlin, pp. 125-140. Lambeck, I.C., Fischer-Schrader, K., Niks, D., Roeper, J., Chi, J.-C., Hille, R. & Schwarz, G. (2012) The mechanism of inhibition of Arabidopsis thaliana nitrate reductase by 14-3-3 protein. J. Biol. Chem. 287, 4562-4571. Hille, R. (2012) The molybdenum-containing hydroxylases and related enzymes. In Molybdenum: Its Biological and Coordination Chemistry (A. Holder and W.E. Newton, eds.) Nova Science Publishers, Happauge, New York. Hillle, R. (2012) Xanthine oxidase and related enzymes. In Encyclopedia of Metalloproteins (R.R. Kretsinger, V.N. Uversky and E.A. Permyakov, eds.), Springer Press. Hille R. (2012) Pyranopterins. In Encyclopedia of Biophysics (V. Davidson, ed.), Springer Press. Anderson, R.F., Shinde, S.S., Maklashina, E., Rajagukguk, S, Hille, R., & Cecchini, G. (2012) Single electron transfers within the flavoprotein succinate:ubiquinone oxidoreductase (Complex II). In Flavins and Flavoproteins (S. Miller, R. Hille, and B. Palfey, eds.) Lulu Press, Raleigh, NC, pp. 209-216. Hille, R., Wilcoxen, J., Zhang, B., and Snider, S. (2012) Kinetic and EPR studies of CO dehydrogenase from Oligotropha carboxidovorans. In Flavins and Flavoproteins (S. Miller, R. Hille, and B. Palfey, eds.) Lulu Press, Raleigh, NC, pp. 217-226. Wilcoxen, J., Zhang, B., & Hille, R. (2012) The oxidative half-reaction of CO dehydrogenase from Oligotropha carboxidovorans. In Flavins and Flavoproteins (S. Miller, R. Hille, and B. Palfey, eds.) Lulu Press, Raleigh, NC, pp. 227-232. Hall, J., Cao, H. & Hille, R. (2012) Cofactor insertion into members of the xanthine oxidase family of molybdenum- and flavin-containing enzymes. In Flavins and Flavoproteins (S. Miller, R. Hille, and B. Palfey, eds.) Lulu Press, Raleigh, NC, pp. 233-238. Niks, D., Spiegelhauer, O., Dobbek, H. & Hille, R. (2012) Characterization of the 2-oxoquinoline monooxygenase reductase component from P. putida 86. In Flavins and Flavoproteins (S. Miller, R. Hille, and B. Palfey, eds.) Lulu Press, Raleigh, NC, pp. 595-600. Hille, R. (2013) The molybdenum oxotransferases and related enzymes. Dalton Trans. 42, 3029-3042.