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|Eduardus (Evert) Duin|
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.
Methyl Coenzyme M Reductase: