4tr3

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

spinqualitylabelsall models 4tr3, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4tr3 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IOD3_MOUSE Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development (By similarity). Publication Abstract from PubMed 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. Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism.,Schweizer U, Schlicker C, Braun D, Kohrle J, Steegborn C Proc Natl Acad Sci U S A. 2014 Jul 7. pii: 201323873. PMID:25002520 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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