研究领域

Biochemistry

Biochemistry: mechanistic enzymology, metalloenzymes, EPR/ESR Isoprene Synthesis and Biodefense Isoprenoids are a group of essential biomolecules present in all organisms, some examples of which are cholesterol, steroid hormones, and ubiquinones. Recently it was discovered that two pathways exists that are used to synthesize isoprenoids, the mevalonate pathway and the DOXP/MEP pathway. In humans and animals isoprenoids are derived from the mevalonate pathway. The DOXP/MEP pathway is the sole pathway in Eubacteria and apicomplexan parasites. Important multi-drug resistant and other pathogens belong to this group, causing for example malaria, tuberculosis, plague, cholera and anthrax. The goal of the proposed research is to fully characterize the proteins involved in the DOXP/MEP pathway and develop inhibitors specific for these proteins as potential anti-infective agents. We recently discovered the final two proteins in the DOXP/MEP pathway, GcpE/IspG and LytB/IspH, both of which contain a highly oxygen-sensitive [4Fe-4S] cluster in their active sites. The goal is to obtain a complete understanding of the reaction mechanism which will enable the development of inhibitors as possible drug candidates. Methyl Coenzyme M Reductase The production of the greenhouse gas methane by methanogenic archaea and the anaerobic activation of methane have long been considered to be separate processes. Recently, however, it was discovered that both processes are catalyzed by the same enzyme: methyl-coenzyme M reductase (MCR). The active site of MCR contains the nickel tetrahydrocorphinoid, cofactor 430 (F430). The long-term goals of our research are to understand the actual mechanism of methane production and the regulation of MCR activity by the cell. A successful outcome will provide important insight into how to slow down livestock methane production and production in rice fields. Both processes contribute to global warming due to the fact that methane is a potent greenhouse gas. Since MCR is also involved in methane activation, understanding the reaction mechanism will provide important information for the design of novel nickel-based catalysts that can perform this function. A process that is very important for the petrochemical industry.

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Prakash, D., Wu, Y., Suh, S.-J., Duin, E.C. (2014) Elucidating the Process of Activation of Methyl-Coenzyme M Reductase. J. Bacteriol., 196, 2491-249 Dhage, P., Samokhvalov, A., Mckee, M.L., Duin,E.C., Tatarchuk, B.J. (2013) Reactive adsorption of hydrogen sulfide by promoted sorbents Cu-ZnO/SiO2: active sites by experiment and simulation. Surface and Interface Analysis, 45, 865-87 Gencic, S., Kelly, K., Ghebreamlak, S., Duin, E.C., Grahame, D.A. (2013) Different Modes of Carbon Monoxide Binding to Acetyl CoA Synthase and the Role of a Conserved Phenylalanine in the Coordination Environment of Nickel. Biochemistry, 52, 1705-171 Lessner, F.H., Jennings, M.E., Hirata, A, Duin, E.C., Lessner, D.J. (2012) Subunit D of RNA polymerase from Methanosarcina acetivorans contains two oxygen-labile [4Fe-4S] clusters: implications for oxidant-dependent regulation of transcription. J. Biol. Chem., 287, 18510-1852 Xu, W., Lees, N.S., Hall, D.*, Welideniya, D., Hoffman, B.M., Duin, E.C. (2012) A closer look at the spectroscopic properties of possible reaction intermediates in WT and mutant (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase (IspH/LytB). Biochemistry, 51, 4835−484 Striegler, S., Dittel, M., Kanso, R., Alonso, N.A., Duin, E.C. (2011) Hydrolysis of glycosides with microgel catalysts. Inorg. Chem., 50, 8869-887 Samokhvalov, A., Duin, E.C., Nair, S., Tatarchuk, B.J. (2011) Adsorption and desorption of dibenzothiophene on Ag-titania studied by the complementary temperature-programmed XPS and ESR. Applied Surface Science, 257, 3226-323 Dhage, P., Samokhvalov, A., Repala, D., Duin, E.C., Tatarchuk, B.J. (2011) Regenerable Fe-Mn-ZnO/SiO2 sorbents for room temperature removal of H2S from fuel reformates: performance, active sites, Operando studies. Physical Chemistry Chemical Physics, 13, 2179-218 Yun, J.Y., Jambovane, S., Kim, S.-K., Cho, S.-H., Duin, E.C., Hong, J.W. (2011) Log-Scale Dose Response of Inhibitors on a Chip. Anal. Chem., 83, 6148-615 Sachin Jambovane, Duck Jong Kim, Evert C. Duin, Se-Kwon Kim, and Jong Wook Hong (2011) Creation of stepwise concentration gradient in picoliter droplets for parallel reactions of Matrix Metalloproteinase II and IX. Anal. Chem., 83, 3358-336 Dhage, P., Samokhvalov, A., Repala, D., Duin, E.C., Bowman, M., Tatarchuk, B.J. (2010) Copper-promoted ZnO/SiO2 regenerable sorbents for the room temperature removal of H2S from reformate gas streams. Ind. Eng. Chem. Res., 49, 8388–839 Samokhvalov, A., Duin, E.C., Nair, S., Bowman, M., Davis, Z., Tatarchuk, B.J. (2010) Study of the surface chemical reactions of thiophene with Ag/Titania by the complementary temperature-programmed electron spin resonance, temperature-programmed desorption, and X-ray photoelectron spectroscopy: Adsorption, desorption, and sorbent regeneration mechanisms. J. Phys. Chem. C, 114, 4075–408 Xu, W., Lees, N.S., Adedeji, D., Wiesner, J., Jomaa, H., Hoffman, B.M., Duin, E.C. (2010) Paramagnetic intermediates of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE/IspG) under steady-state and pre-steady-state conditions. J. Am. Chem. Soc., 132, 14509-1452 Samokhvalov, A., Duin, E.C., Nair, S., Tatarchuk, B.J. (2010) An in situ temperature-programmed XPS study of the surface chemical reactions of thiophene with Ag/titania. Surface and Interface Analysis, 42, 1476-148 Gencic, S., Duin, E.C., Grahame, D.A. (2010) Tight coupling of partial reactions in the acetyl-CoA decarbonylase/synthase (ACDS) multienzyme complex from Methanosarcina thermophila. J.Biol.Chem., 285, 15450-1546 Samokhvalov, A., Nair, S., Duin, E.C., Tatarchuk, B.J. (2010) Surface Characterization of Ag/Titania adsorbents. Appl. Surf. Sci., 256, 3647-365 Jambovane, S.,Duin, E.C., Kim, S.-K., Hong, J.W. (2009) Determination of kinetic parameters, Km and kcat, with a single experiment on a chip. Anal. Chem., 81, 3239 - 324 Rekittke, I., Wiesner, J., Röhrich, R., Demmer, U., Warkentin, E., Xu, W., Troschke, K., Hintz, M., No, J.H., Duin, E.C., Oldfield, E., Jomaa, H., Ermler, U. (2008) Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the terminal enzyme of the non-mevalonate pathway. J. Am. Chem. Soc., 130, 17206-1720 Harmer, J., Finazzo, C., Piskorski, R., Ebner, S., Duin, E.C., Goenrich, M, Thauer, R.K., Reiher, M., Schweiger, A., Hinderberger, D., Jaun, B. (2008) A Nickel Hydride Complex in the Active Site of Methyl-Coenzyme M Reductase: Implications for the Catalytic Cycle, J. Am. Chem. Soc., 130, 10907-1092 Duin, E.C., McKee, M.L. (2008) A New Mechanism for Methane Production from Methyl-Coenzyme M Reductase As Derived from Density Functional Calculations. J. Phys. Chem. B, 112, 2466-2482