Enzymes of tetrapyrrole biosynthesis

The tetrapyrrole biosynthesis is a ubiquitous and central anabolic pathway leading to the formation of essential tetrapyrroles such as heme, chlorophyll and vitamin B12 from simple precursors. In a long-standing collaboration with Dieter Jahn (Technical University Braunschweig) we are systematically investigating the structural and functional elucidation of enzymes belonging to this pathway.

Recent examples are the structures of coproporphyrinogen IX oxidase and aminolevulinic acid synthase.

The O2-independent coproporphyrinogen IX oxidase represents the first structure of an enzyme belonging to the ubiquitous family of "Radical SAM enzymes". Our future goal is to elucidate the catalytic mechanism of this complicated enzyme from structural studies, as well as site-directed mutagenesis and use of synthetic inhibitors (in cooperation with Markus Kalesse, University of Hannover/HZI). (Layer et al, 2006)

Finally we have solved and analyzed the crystal structure of aminolevulinic acid synthase, the first enzyme of tetrapyrrole biosynthesis in mammals and yeast, in complex with both substrates. Mutations in this enzyme lead to rare blood disorders and other diseases. With the structure of aminolevulinic acid synthase the structures of all enzymes of heme biosynthesis have finally been determined.  (Astner et al, 2005).

 Future research will focus on the catalytic mechanism and substrate binding of selected enzymes.



University of Hannover

Technical University Braunschweig

Beteiligte Gruppen

Geldgeber / Förderer


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