个人简介

B.S. (1989), M.S. (1992), Moscow Medical State University 1993-1995 Monbusho scholarship Ph.D. (1995), Inst. for Molecular Science, Okazaki National Research Institutes, Okazaki, Japan Postdoctoral 1995-2001, Michigan State University

研究领域

Analytical Biological Inorganic Physical

(Research Description PDF - 1176 kb) Molecular oxygen, O2 , is a powerful and abundant oxidant. However, the unusual triplet ground state prevents O2 from engaging in spontaneous reactions under ambient conditions, making it uniquely suitable for biology and chemistry. The emergence of organisms capable of controlling O2 reactivity lead to the explosion of aerobic life. We are interested in understanding oxygen activation and controlled utilization of its oxidizing power refined by living cells over billions of years. Details of mechanism-specific control over enzymatic function have broad implications from fundamental chemistry to applied chemical solutions and unlimited biomedical applications. We use a range of spectroscopic, electrochemical, and engineering approaches to resolve structures of bio-inorganic complexes, their reactions with O2, and the ensuing electron transfer. Enzymes use transition metals to overcome spin restrictions of triplet O2 , which oxidizes the metal/protein complex in a concerted, multi-e– step. The resulting highly oxidized species, in turn, initiate chemical reactions with specific substrates. Protein moiety tunes reactivity of the metal through coordination environment and accessibility. Eukaryotic cells generate majority of chemical energy in mitochondria: semi-autonomous organelles, which capture the energy of e– current from food to O2 to make ATP. A chain of coupled redox reactions is catalyzed by enzyme complexes spanning inner mitochondrial membrane. Native inner membrane is impermeable for H+ and most metabolites. Inner membrane isolates mitochondria from the cytosol and greatly limits functional studies on whole mitochondria. We are developing a fundamentally new method to study intact mitochondria. It is based on dynamic redox equilibrium of natural metabolites, membrane transport, and electrochemistry on specifically modified electrodes. We establish chemically-mediated e– current from fiber electrodes into mitochondrial enzymes and further to oxygen, mimicking natural metabolic pathways as an artificial “respiration in a tube”. An enzyme from methanotropic bacteria uses a pair of highly oxidized FeIV ions to accomplish an unrivaled conversion of methane to methanol. Detailed mechanism of this reaction is of major interest for converting natural gas to liquid fuels and as an initial step in the industrial synthesis. Enzymatic O2 activation always involves reduction, or binding of a reducing cofactor, followed by metal oxidation (top). The formal FeV=O activates the substrate SH to transient S? radical, which recombines with hydroxyl radical to yield the product and to re-generate FeIII. By reversing the reaction under large positive electrode potential we can generate FeV=O directly from water, thus circumventing the need for either O2 or the initial reduction of the metal (bottom).

近期论文

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Apoprotein isolation and activation, and vibrational structure of the Helicobacter mustelae iron urease, Carter E.L., Proshlyakov, D.A., Hausinger, R.P., J. Inorg. Biochem. 2012, 111, 195. Transient iron species in the catalytic mechanism of the archetypal α-ketoglutarate-dependent dioxygenase in Iron-containing enzymes: versatile catalysts of hydroxylation reactions in nature, Proshlyakov, D.A., & Hausinger, R.P; de Visser, S., & Kumar, D, Eds., RSC, 2011. Characterization of metal and substrate binding to an Fe(II) dioxygenase by UV absorption, Grzyska, P.K., Hausinger, R.P., Proshlyakov, D.A., Anal. Biochem. 2010, 399(1), 64. Equilibrium and Kinetic Behavior of Fe(CN)63–/4– and Cytochrome c in Direct Electrochemistry using a Film Electrode Thin-Layer Transmission Cell, Dai, Y., Zheng, Y., Greg M. Swain, G.M., Proshlyakov, D.A., Anal. Chem. 2010, 83(2), 542. Insight into the mechanism of an iron dioxygenase by resolution of steps following the FeIV=O species, Grzyska, P.K., Appelman, E.H., Hausinger R.P., Proshlyakov, D.A., Proc. Natl. Acad. Sci. U.S.A. 2010, 107(9), 3982.