Structural Insights into the Iodothyronine Deiodinase 2 Catalytic Core and Deiodinase Catalysis and Dimerization.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Iodide Peroxidase*/chemistry ; Iodide Peroxidase*/metabolism ; Iodide Peroxidase*/genetics ; Catalytic Domain* ; Protein Multimerization*; Animals ; Mice ; Iodothyronine Deiodinase Type II ; Models, Molecular ; Crystallography, X-Ray ; Biocatalysis ; Dimerization ; Catalysis

Iodothyronine deiodinases (Dio) are selenocysteine-containing membrane enzymes that activate and inactivate the thyroid hormones (TH) through reductive iodide eliminations. The three deiodinase isoforms are homodimers sharing highly conserved amino acid sequences, but they differ in their regioselectivities for the deiodination reaction and regulatory features. We have now solved a crystal structure of the mouse deiodinase 2 (Dio2) catalytic domain. It reveals a high overall similarity to the deiodinase 3 structure, supporting the proposed common mechanism, but also Dio2-specific features, likely mediating its unique properties. Activity studies with an artificially enforced Dio dimer further confirm that dimerization is required for activity and requires both the catalytic core and the enzyme's N-terminus. Cross-linking studies reveal the catalytic core's dimerization interface, providing insights into the architecture of the complete, active Dio homodimer.

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SCHW914/6-1 Deutsche Forschungsgemeinschaft; STE1701/16-1 Deutsche Forschungsgemeinschaft; I-1355-302.5/2016 German-Israeli Fund; funding to US University Hospital Bonn; SCIMED program University Hospital Bonn

Keywords: activity; cross-linking; crystal structure; dimerization interface; substrate binding; type II iodothyronine deiodinase

EC 1.11.1.8 (Iodide Peroxidase)
EC 1.11.1.- (Iodothyronine Deiodinase Type II)

Date Created: 20241127 Date Completed: 20241127 Latest Revision: 20241130

20241202

PMC11592359

10.3390/biom14111373

39595550