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February 2012
Identifying structure: mobile C-terminal arm of thioredoxin reductase (hTrxR1)
hTrxR-Dimer (grey) with bonded hTrx1 (blue). FAD is shown in
yellow, the N-terminal redox centre in red. Different positions of the
C-terminal arm are shown in pink, orange and green.
The
homodimerous NADPH-dependent flavoenzyme thioredoxinreductase (hTrxR1)
is one of only 25 human selenocysteine-containing enzymes and involved
in numerous redox associated processes. It is highly expressed in many
tumors, therefore it is in the focus of many research groups.
After crystallization of the enzyme 4 years ago, the team of Prof. Becker now developed a structural concept of the spatial organization of the enzyme during electron transport: the C-terminal arm containing selenocysteine was hypothesized to be mobile.
Recently, a more detailed insight could be gained using a
hTrxR1-thioredoxin crystal complex after intelligent selection of
mutants. This way, the hypothesis of a mobile C-terminal arm could be
validated. Furthermore, amino acids involved in the binding between TrxR
and Trx could be verified by targeted mutagenesis. Now, this complex
structure serves as basis for rational development of pharmaceuticals,
particularly in cancer therapy.
Contact:
Prof. Dr. Katja Becker, Nutritional Biochemistry
06.12.2012 14:09
