2j4a

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{{Seed}}
 
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[[Image:2j4a.png|left|200px]]
 
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==Human Thyroid hormone receptor beta ligand binding domain in complex with KB131084==
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The line below this paragraph, containing "STRUCTURE_2j4a", creates the "Structure Box" on the page.
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<StructureSection load='2j4a' size='340' side='right'caption='[[2j4a]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2j4a]] is a 1 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=2J4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J4A FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OEF:3,5-DIBROMO-4-(3-ISOPROPYL-PHENOXY)BENZOIC+ACID'>OEF</scene></td></tr>
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{{STRUCTURE_2j4a| PDB=2j4a | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2j4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j4a OCA], [https://pdbe.org/2j4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j4a RCSB], [https://www.ebi.ac.uk/pdbsum/2j4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j4a ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN] Defects in THRB are the cause of generalized thyroid hormone resistance (GTHR) [MIM:[https://omim.org/entry/188570 188570]. GTHR is a disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH).<ref>PMID:2510172</ref> <ref>PMID:2153155</ref> <ref>PMID:1846005</ref> <ref>PMID:1661299</ref> <ref>PMID:1653889</ref> <ref>PMID:1563081</ref> <ref>PMID:1314846</ref> <ref>PMID:1619012</ref> <ref>PMID:1587388</ref> <ref>PMID:1324420</ref> <ref>PMID:8514853</ref> <ref>PMID:8175986</ref> <ref>PMID:7833659</ref> <ref>PMID:8664910</ref> <ref>PMID:8889584</ref> <ref>PMID:10660344</ref> <ref>PMID:16804041</ref> <ref>PMID:19268523</ref> Defects in THRB are the cause of generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:[https://omim.org/entry/274300 274300]. An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. Defects in THRB are the cause of selective pituitary thyroid hormone resistance (PRTH) [MIM:[https://omim.org/entry/145650 145650]; also known as familial hyperthyroidism due to inappropriate thyrotropin secretion. PRTH is a variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established.<ref>PMID:7528740</ref> <ref>PMID:8381821</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN] High affinity receptor for triiodothyronine.<ref>PMID:17418816</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j4/2j4a_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j4a ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A new high-affinity thyroid hormone antagonist 6 with druglike properties was designed and synthesized. The compound behaved as an antagonist in a cell transactivation assay, and in a first in vivo experiment in rats.
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===HUMAN THYROID HORMONE RECEPTOR BETA LIGAND BINDING DOMAIN IN COMPLEX WITH KB131084===
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Thyroid receptor ligands. 6. A high affinity "direct antagonist" selective for the thyroid hormone receptor.,Koehler K, Gordon S, Brandt P, Carlsson B, Backsbro-Saeidi A, Apelqvist T, Agback P, Grover GJ, Nelson W, Grynfarb M, Farnegardh M, Rehnmark S, Malm J J Med Chem. 2006 Nov 16;49(23):6635-7. PMID:17154490<ref>PMID:17154490</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2j4a" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17154490}}, adds the Publication Abstract to the page
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*[[Thyroid hormone receptor 3D structures|Thyroid hormone receptor 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17154490 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17154490}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2J4A is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J4A OCA].
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==Reference==
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Thyroid receptor ligands. 6. A high affinity "direct antagonist" selective for the thyroid hormone receptor., Koehler K, Gordon S, Brandt P, Carlsson B, Backsbro-Saeidi A, Apelqvist T, Agback P, Grover GJ, Nelson W, Grynfarb M, Farnegardh M, Rehnmark S, Malm J, J Med Chem. 2006 Nov 16;49(23):6635-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17154490 17154490]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Farnegardh, M.]]
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[[Category: Farnegardh M]]
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[[Category: Alternative splicing]]
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[[Category: Deafness]]
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[[Category: Disease mutation]]
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[[Category: Dna-binding]]
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[[Category: Ligand binding domain]]
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[[Category: Metal-binding]]
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[[Category: Nuclear protein]]
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[[Category: Nuclear receptor]]
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[[Category: Polymorphism]]
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[[Category: Receptor]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Zinc]]
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[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:37:40 2008''
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Current revision

Human Thyroid hormone receptor beta ligand binding domain in complex with KB131084

PDB ID 2j4a

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