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| | ==Crystal structure of haliscomenobacter hydrossis iodotyrosine deiodinase (IYD) bound to FMN and mono-iodotyrosine (I-Tyr)== | | ==Crystal structure of haliscomenobacter hydrossis iodotyrosine deiodinase (IYD) bound to FMN and mono-iodotyrosine (I-Tyr)== |
| - | <StructureSection load='5ko8' size='340' side='right' caption='[[5ko8]], [[Resolution|resolution]] 2.15Å' scene=''> | + | <StructureSection load='5ko8' size='340' side='right'caption='[[5ko8]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ko8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KO8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ko8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Haliscomenobacter_hydrossis_DSM_1100 Haliscomenobacter hydrossis DSM 1100]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KO8 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=IYR:3-IODO-TYROSINE'>IYR</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]] 2.15Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ko7|5ko7]]</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=IYR:3-IODO-TYROSINE'>IYR</scene></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=5ko8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko8 OCA], [http://pdbe.org/5ko8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ko8 RCSB], [http://www.ebi.ac.uk/pdbsum/5ko8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko8 ProSAT]</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=5ko8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ko8 OCA], [https://pdbe.org/5ko8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ko8 RCSB], [https://www.ebi.ac.uk/pdbsum/5ko8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ko8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/IYD_HALH1 IYD_HALH1] Catalyzes the dehalogenation of halotyrosines such as 3-iodo-L-tyrosine and 3,5-diiodo-L-tyrosine (PubMed:24153409, PubMed:28157283). Likely to also catalyze the dehalogenation of other halotyrosines such as 3-bromo-L-tyrosine, 3-chloro-L-tyrosine and 3-iodo-L-tyrosine (By similarity). Activity towards 3-iodo-L-tyrosine is much stronger than activity towards 3,5-diiodo-L-tyrosine and 2-iodophenol (PubMed:28157283, PubMed:24153409).[UniProtKB:B9K712]<ref>PMID:24153409</ref> <ref>PMID:28157283</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 5ko8" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5ko8" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Nitroreductase 3D structures|Nitroreductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ingavat, N]] | + | [[Category: Haliscomenobacter hydrossis DSM 1100]] |
| - | [[Category: Kavran, J M]] | + | [[Category: Large Structures]] |
| - | [[Category: Rokita, S E]] | + | [[Category: Ingavat N]] |
| - | [[Category: Sun, Z]] | + | [[Category: Kavran JM]] |
| - | [[Category: Flavin mononucleotide]] | + | [[Category: Rokita SE]] |
| - | [[Category: Haliscomenobacter hydrossis]] | + | [[Category: Sun Z]] |
| - | [[Category: Iodotyrosine deiodinase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
IYD_HALH1 Catalyzes the dehalogenation of halotyrosines such as 3-iodo-L-tyrosine and 3,5-diiodo-L-tyrosine (PubMed:24153409, PubMed:28157283). Likely to also catalyze the dehalogenation of other halotyrosines such as 3-bromo-L-tyrosine, 3-chloro-L-tyrosine and 3-iodo-L-tyrosine (By similarity). Activity towards 3-iodo-L-tyrosine is much stronger than activity towards 3,5-diiodo-L-tyrosine and 2-iodophenol (PubMed:28157283, PubMed:24153409).[UniProtKB:B9K712][1] [2]
Publication Abstract from PubMed
The minimal requirements for substrate recognition and turnover by iodotyrosine deiodinase were examined to learn the basis for its catalytic specificity. This enzyme is crucial for iodide homeostasis and the generation of thyroid hormone in chordates. 2-Iodophenol binds only very weakly to the human enzyme and is dehalogenated with a kcat/Km that is more than 4 orders of magnitude lower than that for iodotyrosine. This discrimination likely protects against a futile cycle of iodinating and deiodinating precursors of thyroid hormone biosynthesis. Surprisingly, a very similar catalytic selectivity was expressed by a bacterial homologue from Haliscomenobacter hydrossis. In this example, discrimination was not based on affinity since 4-cyano-2-iodophenol bound to the bacterial deiodinase with a Kd lower than that of iodotyrosine and yet was not detectably deiodinated. Other phenols including 2-iodophenol were deiodinated but only very inefficiently. Crystal structures of the bacterial enzyme with and without bound iodotyrosine are nearly superimposable and quite similar to the corresponding structures of the human enzyme. Likewise, the bacterial enzyme is activated for single electron transfer after binding to the substrate analogue fluorotyrosine as previously observed with the human enzyme. A cocrystal structure of bacterial deiodinase and 2-iodophenol indicates that this ligand stacks on the active site flavin mononucleotide (FMN) in a orientation analogous to that of bound iodotyrosine. However, 2-iodophenol association is not sufficient to activate the FMN chemistry required for catalysis, and thus the bacterial enzyme appears to share a similar specificity for halotyrosines even though their physiological roles are likely very different from those in humans.
Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase.,Ingavat N, Kavran JM, Sun Z, Rokita SE Biochemistry. 2017 Feb 28;56(8):1130-1139. doi: 10.1021/acs.biochem.6b01308. Epub, 2017 Feb 16. PMID:28157283[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Phatarphekar A, Buss JM, Rokita SE. Iodotyrosine deiodinase: a unique flavoprotein present in organisms of diverse phyla. Mol Biosyst. 2014 Jan;10(1):86-92. PMID:24153409 doi:10.1039/c3mb70398c
- ↑ Ingavat N, Kavran JM, Sun Z, Rokita SE. Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase. Biochemistry. 2017 Feb 28;56(8):1130-1139. doi: 10.1021/acs.biochem.6b01308. Epub, 2017 Feb 16. PMID:28157283 doi:http://dx.doi.org/10.1021/acs.biochem.6b01308
- ↑ Ingavat N, Kavran JM, Sun Z, Rokita SE. Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase. Biochemistry. 2017 Feb 28;56(8):1130-1139. doi: 10.1021/acs.biochem.6b01308. Epub, 2017 Feb 16. PMID:28157283 doi:http://dx.doi.org/10.1021/acs.biochem.6b01308
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