Biochemistry Department

Russ Hille

Dr. Russ Hille

Russ Hille
Distinguished Professor of Biochemistry

Enzymology, Physical Biochemistry, Molecular Biophysics

Hille Research Group
PubMed Citations


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.

Current research interests
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.


Awards and Honors
  • 2011-2012  Humboldt Research Prize, Alexander von Humboldt Foundation
  • 2008  Wenner-Gren Foundation, Fellowship
  • 2007  Chancelor’s Professor, University of California, Riverside
  • 2004  Fellow of the American Association for the Advancement of Science
  • 2003-2004  Humbolt Research Prize, Alexander von Humboldt Foundation
  • 1997  Simson Faculty Research Award, The Ohio State University
Selected Publications
  •   Niks, D, Duvvuru, J., Escalona, M. & Hille, R. (2016) Spectrosccopic and kinetic characterization of the soluble, NAD+-dependent formate dehydrogenase from Ralstonia eutrophaJ. 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. Sign23, 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.
  • Tejero, J., Biswas, A., Haque, M.M., Wang, Z.-Q., Hemann, C., Varnado, C.L., Novince, Z., Hille, R., Goodwin, D.C. & Stuehr, D.J. (2011) Mesoheme-substitution reveals how heme electronic properties can influence the kinetic and catalytic parameters of neuronal NO synthase. Biochem. J. 433, 163-174.
  • Service, R.J., Yano, J., McConnell, I., Hwang, H.J., Niks, D., Hille, R., Wydrzynski, T., Burnap, R.L., Hillier, W., & Debus, R.J. (2011) Participation of glutamate-354 of the CP43 in the ligation of Mn and the binding of substrate water in photosystem II. Biochemistry 50, 63-81.
  • Havelius, K.G.V., Reschke, S., Horn, S., Döring, A., Niks, D., Hille, R., Schulzke, C., Leimkühler, S., & Haumann, M. (2011) The structure of the molybdenum site of YedY, a sulfite oxidase homologue from Escherichia coli. Inorg. Chem. 50, 741-748.
  • Wilcoxen, J., Zhang, B. & Hille, R. (2011) The oxidative half-reaction of the molybdenum-copper CO dehydrogenase from Oligotropha carboxidovorans. Biochemistry 50, 1910-1916.
  • Mtei, R., Lyashenko, G., Stein, B., Rubie, N., Hille, R. and Kirk, M.L. (2011) Spectroscopic and electronic structure studies of a DMSO reductase catalytic intermediate: implications for electron and atom transfer reactivity. J. Am. Chem. Soc. 133, 9762-9774.
  • Cao, H., Hall, J. & Hille, R. (2011) X-ray crystal structure of arsenite-inhibited xanthine oxidase: µ-sulfido µ-oxo double bridge between molybdenum and arsenic in the active site. J. Am. Chem. Soc. 133, 12414-12417.
  • Wilcoxen, J., Snider, S., & Hille, R. (2011) Substitution of silver for copper in the binuclear Mo/Cu cluster of CO dehydrogenase leads to partial retention of catalytic power. J. Am. Chem. Soc., 133, 12934-12936.
  • Hille, R. (2011) Arsenite oxidase: molecular, biological and environmental aspects. in Handbook of Metalloproteins Vols 4&5 (A. Messerschmidt, ed.), John Wiley & Sons, Ltd, Chichester, UK, pp. 533-540.
  • R. Hille & R.R. Mendel (2011) An overview of molybdenum in biology. Coord. Chem. Rev. 255, 991-992.
  • Hille, R., Nishino, T., and Bittner, F. (2011) Eukaryotic molybdenum enzymes. Coord. Chem. Rev. 255, 1179-1205.
  • Zhang, B., Hemann, C.F., & Hille, R. (2010) Kinetic and spectroscopic studies of the molybdenum-copper CO dehydrogenase from Oligotropha carboxidovorans. J. Biol. Chem., 285, 12571-12578.
  • Duval, S., Santini, J.M., Nitschke, W., Hille, R., & Schoepp-Cothenet, B. (2010) The small AroB subunit of arsenite oxidase: Lessons on the [2Fe-2S] Rieske protein superfamily. J. Biol. Chem. 285, 20442-20451.
  • Cao, H., Pauff, J.M., & Hille, R. (2010) Substrate orientation and catalytic specificity of xanthine oxidase: strictly ordered hydroxylation steps from hypoxanthine to uric acid., J. Biol. Chem. 285, 28044-28053.
  • Wahl, B., Reichmann, D., Niks, D., Biester, H., Krompholz, N., Havemeyer, A., Clement, B., Meßerschmidt, T., Rothkegel, M., Hille, R.,Mendel, R.R., & Bittner, F. (2010) Biochemical and spectroscopic characterization of the human mitochondrial amidoxime-reducing components hmARC-1 and hmARC-2 suggests the existence of a new molybdenum enzyme family in eukaryotes. J. Biol. Chem. 285, 37847-37859.
  • Shanmugam, M., Zhang, B., McNaughton, R.L., Kinney, A., Hille, R. & Hoffman, B.M. (2010) The structure of formaldehyde-inhibited xanthine oxidase determined by 35 GHz 2H ENDOR spectroscopy. J. Am. Chem. Soc. 132, 14015-14017.
  • Hille, R. (2010) EPR studies of xanthine oxidoreductase and other molybdenum-containing hydroxylases Ch. 5. in Biological Magnetic Resonance vol. 29, Metals in Biology: Applications of High-Resolution EPR to Metalloenzymes. (G. Hanson and L. Berliner, Jr., eds.) Springer, Berlin, pp. 91-121.
  • Cao, H., Pauff, J.M., & Hille, R. (2010) Substrate Binding and Orientation in Xanthine Oxidase. Indian J. Chem. 50A, 355-362.


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