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| | ==The crystal structure of human IYD Thr239 mutant with ligand 3-Fluorotyrosine (F-Tyr)== | | ==The crystal structure of human IYD Thr239 mutant with ligand 3-Fluorotyrosine (F-Tyr)== |
| - | <StructureSection load='5yak' size='340' side='right' caption='[[5yak]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='5yak' size='340' side='right'caption='[[5yak]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yak]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YAK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yak]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YAK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=YOF:3-FLUOROTYROSINE'>YOF</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IYD, C6orf71, DEHAL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=YOF:3-FLUOROTYROSINE'>YOF</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Iodotyrosine_deiodinase Iodotyrosine deiodinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.21.1.1 1.21.1.1] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5yak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yak OCA], [https://pdbe.org/5yak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yak RCSB], [https://www.ebi.ac.uk/pdbsum/5yak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yak ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5yak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yak OCA], [http://pdbe.org/5yak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yak RCSB], [http://www.ebi.ac.uk/pdbsum/5yak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yak ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/IYD1_HUMAN IYD1_HUMAN]] Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/IYD1_HUMAN IYD1_HUMAN] Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IYD1_HUMAN IYD1_HUMAN]] Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. Acts more efficiently on monoiodotyrosine than on diiodotyrosine.<ref>PMID:15289438</ref> | + | [https://www.uniprot.org/uniprot/IYD1_HUMAN IYD1_HUMAN] Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. Acts more efficiently on monoiodotyrosine than on diiodotyrosine.<ref>PMID:15289438</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5yak" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5yak" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dehalogenase 3D structures|Dehalogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Iodotyrosine deiodinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Hu, J M]] | + | [[Category: Hu JM]] |
| - | [[Category: Rokita, S E]] | + | [[Category: Rokita SE]] |
| - | [[Category: Schlessman, J]] | + | [[Category: Schlessman J]] |
| - | [[Category: Fmn]]
| + | |
| - | [[Category: Hiyd]]
| + | |
| - | [[Category: Mft]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: T239a mutant]]
| + | |
| Structural highlights
Disease
IYD1_HUMAN Familial thyroid dyshormonogenesis. The disease is caused by mutations affecting the gene represented in this entry.
Function
IYD1_HUMAN Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. Acts more efficiently on monoiodotyrosine than on diiodotyrosine.[1]
Publication Abstract from PubMed
The redox chemistry of flavoproteins is often gated by substrate and iodotyrosine deiodinase (IYD) has the additional ability to switch between reaction modes based on substrate. Association of fluorotyrosine (F-Tyr), an inert substrate analog, stabilizes single electron transfer reactions of IYD that are not observed in the absence of this ligand. The co-crystal of F-Tyr and a T239A variant of human IYD has now been characterized to provide a structural basis for control of its flavin reactivity. Coordination of F-Tyr in the active site of this IYD closely mimics that of iodotyrosine and only minor perturbations are observed after replacement of an active site Thr with Ala. However, loss of the side chain hydroxyl group removes a key hydrogen bond from flavin and suppresses formation of its semiquinone intermediate. Even substitution of Thr with Ser decreases the midpoint potential of human IYD between its oxidized and semiquinone forms of flavin by almost 80 mV. This decrease does not adversely affect the kinetics of reductive dehalogenation although an analogous Ala variant exhibits a 6.7-fold decrease in its kcat /Km . Active site ligands lacking the zwitterion of halotyrosine are not able to induce closure of the active site lid that is necessary for promoting single electron transfer and dehalogenation. Under these conditions, a basal two electron process dominates catalysis as indicated by preferential reduction of nitrophenol rather than deiodination of iodophenol. This article is protected by copyright. All rights reserved.
Redox control of iodotyrosine deiodinase.,Hu J, Su Q, Schlessman J, Rokita SE Protein Sci. 2018 Jul 27. doi: 10.1002/pro.3479. PMID:30052294[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gnidehou S, Caillou B, Talbot M, Ohayon R, Kaniewski J, Noel-Hudson MS, Morand S, Agnangji D, Sezan A, Courtin F, Virion A, Dupuy C. Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site. FASEB J. 2004 Oct;18(13):1574-6. Epub 2004 Aug 2. PMID:15289438 doi:http://dx.doi.org/10.1096/fj.04-2023fje
- ↑ Hu J, Su Q, Schlessman J, Rokita SE. Redox control of iodotyrosine deiodinase. Protein Sci. 2018 Jul 27. doi: 10.1002/pro.3479. PMID:30052294 doi:http://dx.doi.org/10.1002/pro.3479
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