Elucidation of the binding of the C1 carrier, tetrahydromethanopterin, and its derivatives, to enzymes involved in the energy metabolism pathway of methanogenic archaea

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In methanogenic and sulfate-reducing archaea tetrahydromethanopterin (H4MPT) acts as a C1 carrier between formyl and methyl oxidation levels. It is a coenzyme in many enzymatic reactions and is structurally analogous to tetrahydrofolate (h4F) - the C1 carrier in most other organisms. This project aims to study the binding of tetrahydromethanopterin, and its derivatives, to enzymes involved in the energy metabolism pathway of methanogenic archaea. The major emphasis will be towards solving the structure of the enzyme-coenzyme complexis by X-ray crystallography. These structures are expected to give important insight into the binding sites of the coenzyme and thus, into the mechanism of many enzymatic reactions critical to methanogenesis. Three enzymes - the methenly-H4MPT cyclohydrolase, the formylmethanofuran:H4MPT formyltransferase and the methyl-H4MPT:coenzyme M methyltransferase - from the methanogenic pathway have been chosen for this study. Additionally, the project aims to develop a fluorimetric assay for coenzyme bindung to these enzymes. Detailed description of aims, methods, wirk plan and time schedule are given separately.