Priority Programme: THYROID TRANS ACT
Translation of Thyroid Hormone Actions beyond Classical Concepts

Prof. Dr. Ulrich Schweizer, Prof. Dr. Clemens Steegborn

Biochemical and structural characterization of mammalian deiodinases as key regulators of thyroid hormone metabolism

Thyroxine (T4) is the major secreted product of the thyroid gland. Through site specific deiodination, T4 is converted to T3, the receptor-binding hormone. An additional deiodination step from T3 to T2 leads to inactivation. Deiodination and decarboxylation of thyroid hormones (TH) further lead to formation of thyronamines, TAM. All these TH deiodinations are catalyzed by a family of three iodothyronine deiodinase (Dio) isoforms (Dio1, Dio2, Dio3), which differ in their regioselectivity among the two aromatic rings of TH. The deiodinases form an evolutionary family sharing significant sequence homology and most architectural and catalytic properties. They contain selenocysteine (Sec) in their active sites and an N-terminal transmembrane region that contributes to dimerization, which is essential for deiodinase activity. As key enzymes in TH metabolism, Dio enzymes appear to be attractive drug targets, and the development of isoenzyme-specific inhibitors would be desirable from the perspective of clinical use.

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Project Coordinator(s):

Prof. Dr. Ulrich Schweizer
Rheinische Friedrich-Wilhelms-Universität Bonn
Institut für Biochemie und Molekularbiologie
Nussallee 11
53115 Bonn
Phone: +49 228 73 4444
uschweiz@uni-bonn.de

Prof. Dr. Clemens Steegborn
University of Bayreuth
Dept. Biochemistry, NW III
Universitaetsstr. 30
95447 Bayreuth
Phone: +49 921 557 831
clemens.steegborn@uni-bayreuth.de