Crystal structure of mammalian selenocysteinedependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism

Ulrich Schweizer; Christine Schlicker; Doreen BraunJosef K?hrleClemens Steegborn

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Crystal structure of mammalian selenocysteinedependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism

机译：Crystal structure of mammalian selenocysteinedependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism

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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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第29期|10526-10531|共6页
作者
Ulrich Schweizer; Christine Schlicker; Doreen BraunJosef K?hrleClemens Steegborn;
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作者单位

Department of Physiological Chemistry, Ruhr University Bochum, 44801 Bochum, Germany;

Institut für Biochemie und Molekularbiologie, Rheinische Friedrich Wilhelms-Universit?t Bonn, 53115 Bonn, Germany;

Institut für Experimentelle Endokrinologie, Charité-Universit?tsmedizin Berlin, 13353 Berlin, GermanyDepartment of Biochemistry and Research Center for Bio-Macromolecules, University of Bayreuth, 95440 Bayreuth, Germany;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
iodothyronine deiodination; thioredoxin fold; selenoprotein; thiol cofactor; selenenyl-sulfide;

Crystal structure of mammalian selenocysteinedependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism

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