9H48

Mouse Iodothyronine deiodinase 2 catalytic core, mutant - LysLys180AlaAla, Secys-> Cys

Summary for 9H48

• Entry DOI: 10.2210/pdb9h48/pdb
• Related: 4TR4
• Descriptor: Type II iodothyronine deiodinase (2 entities in total)
• Functional Keywords: thioredoxin-fold, iodothyronine deiodinase, oxidoreductase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 21347.76

Authors

Towell, H.,Steegborn, C. (deposition date: 2024-10-17, release date: 2024-12-11)

Primary citation

Towell, H.,Braun, D.,Brol, A.,di Fonzo, A.,Rijntjes, E.,Kohrle, J.,Schweizer, U.,Steegborn, C.
Structural Insights into the Iodothyronine Deiodinase 2 Catalytic Core and Deiodinase Catalysis and Dimerization.
Biomolecules, 14:-, 2024

PubMed Abstract: 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.

PubMed: 39595550
DOI: 10.3390/biom14111373

Experimental method

X-RAY DIFFRACTION (1.09 Å)