Document Type
Article
Publication Date
2020
DOI
10.1038/s41598-020-72243-9
Publication Title
Scientific Reports
Volume
10
Pages
10 pp.
Abstract
Iodothyronine deiodinases (Dios) are important selenoproteins that control the concentration of the active thyroid hormone (TH) triiodothyronine through regioselective deiodination. The X-ray structure of a truncated monomer of Type III Dio (Dio3), which deiodinates TH inner rings through a selenocysteine (Sec) residue, revealed a thioredoxin-fold catalytic domain supplemented with an unstructured Ω-loop. Loop dynamics are driven by interactions of the conserved Trp207 with solvent in multi-microsecond molecular dynamics simulations of the Dio3 thioredoxin(Trx)-fold domain. Hydrogen bonding interactions of Glu200 with residues conserved across the Dio family anchor the loop's N-terminus to the active site Ser-Cys-Thr-Sec sequence. A key long-lived loop conformation coincides with the opening of a cryptic pocket that accommodates thyroxine (T4) through an I…Se halogen bond to Sec170 and the amino acid group with a polar cleft. The Dio3-T4 complex is stabilized by an I…O halogen bond between an outer ring iodine and Asp211, consistent with Dio3 selectivity for inner ring deiodination. Non-conservation of residues, such as Asp211, in other Dio types in the flexible portion of the loop sequence suggests a mechanism for regioselectivity through Dio type-specific loop conformations. Cys168 is proposed to attack the selenenyl iodide intermediate to regenerate Dio3 based upon structural comparison with related Trx-fold proteins.
Original Publication Citation
Bayse, C. A., Marsan, E. S., Garcia, J. R., & Tran-Thompson, A. T. (2020). Thyroxine binding to type III iodothyronine deiodinase. Scientific reports, 10, 1-10, Article 15401. https://doi.org/10.1038/s41598-020-72243-9
ORCID
0000-0002-3490-576X (Bayse)
Repository Citation
Bayse, Craig A.; Marsan, Eric S.; Garcia, Jenna R.; and Tran-Thompson, Alexis T., "Thyroxine Binding to Type III Iodothyronine Deiodinase" (2020). Chemistry & Biochemistry Faculty Publications. 192.
https://digitalcommons.odu.edu/chemistry_fac_pubs/192
Comments
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