4TR4

Mouse iodothyronine deiodinase 3 catalytic core, active site mutant SeCys->Cys

4TR4 の概要

• エントリーDOI: 10.2210/pdb4tr4/pdb
• 関連するPDBエントリー: 4TR3
• 分子名称: Type III iodothyronine deiodinase (2 entities in total)
• 機能のキーワード: oxidoreductase, thyronine hormones, thioredoxin fold
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cell membrane ; Single-pass type II membrane protein : Q91ZI8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21509.06

構造登録者

Steegborn, C.,Schweizer, U.,Schlicker, C. (登録日: 2014-06-13, 公開日: 2014-07-23, 最終更新日: 2023-12-20)

主引用文献

Schweizer, U.,Schlicker, C.,Braun, D.,Kohrle, J.,Steegborn, C.
Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism.
Proc.Natl.Acad.Sci.USA, 111:10526-, 2014

PubMed Abstract: Local levels of active thyroid hormone (3,3',5-triiodothyronine) are controlled by the action of activating and inactivating iodothyronine deiodinase enzymes. Deiodinases are selenocysteine-dependent membrane proteins catalyzing the reductive elimination of iodide from iodothyronines through a poorly understood mechanism. We solved the crystal structure of the catalytic domain of mouse deiodinase 3 (Dio3), which reveals a close structural similarity to atypical 2-Cys peroxiredoxin(s) (Prx). The structure suggests a route for proton transfer to the substrate during deiodination and a Prx-related mechanism for subsequent recycling of the transiently oxidized enzyme. The proposed mechanism is supported by biochemical experiments and is consistent with the effects of mutations of conserved amino acids on Dio3 activity. Thioredoxin and glutaredoxin reduce the oxidized Dio3 at physiological concentrations, and dimerization appears to activate the enzyme by displacing an autoinhibitory loop from the iodothyronine binding site. Deiodinases apparently evolved from the ubiquitous Prx scaffold, and their structure and catalytic mechanism reconcile a plethora of partly conflicting data reported for these enzymes.

PubMed: 25002520
DOI: 10.1073/pnas.1323873111

実験手法

X-RAY DIFFRACTION (1.93 Å)