1n46

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{{STRUCTURE_1n46| PDB=1n46 | SCENE= }}
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==CRYSTAL STRUCTURE OF HUMAN TR BETA LIGAND-BINDING DOMAIN COMPLEXED WITH A POTENT SUBTYPE-SELECTIVE THYROMIMETIC==
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===CRYSTAL STRUCTURE OF HUMAN TR BETA LIGAND-BINDING DOMAIN COMPLEXED WITH A POTENT SUBTYPE-SELECTIVE THYROMIMETIC===
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<StructureSection load='1n46' size='340' side='right' caption='[[1n46]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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{{ABSTRACT_PUBMED_12565933}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1n46]] is a 2 chain structure with 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=1N46 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N46 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PFA:[4-(4-HYDROXY-3-ISOPROPYL-PHENOXY)-3,5-DIMETHYL-PHENYL]-6-AZAURACIL'>PFA</scene><br>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n46 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1n46 RCSB], [http://www.ebi.ac.uk/pdbsum/1n46 PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN]] Defects in THRB are the cause of generalized thyroid hormone resistance (GTHR) [MIM:[http://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:[http://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:[http://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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[[http://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/n4/1n46_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/chain_selection.php?pdb_ID=2ata 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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In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TR beta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis.
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==Disease==
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Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TR beta subtype-selective thyromimetics.,Dow RL, Schneider SR, Paight ES, Hank RF, Chiang P, Cornelius P, Lee E, Newsome WP, Swick AG, Spitzer J, Hargrove DM, Patterson TA, Pandit J, Chrunyk BA, LeMotte PK, Danley DE, Rosner MH, Ammirati MJ, Simons SP, Schulte GK, Tate BF, DaSilva-Jardine P Bioorg Med Chem Lett. 2003 Feb 10;13(3):379-82. PMID:12565933<ref>PMID:12565933</ref>
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[[http://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN]] Defects in THRB are the cause of generalized thyroid hormone resistance (GTHR) [MIM:[http://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:[http://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:[http://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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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN]] High affinity receptor for triiodothyronine.<ref>PMID:17418816</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[1n46]] is a 2 chain structure with 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=1N46 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:012565933</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ammirati, M J.]]
[[Category: Ammirati, M J.]]

Revision as of 16:50, 29 September 2014

CRYSTAL STRUCTURE OF HUMAN TR BETA LIGAND-BINDING DOMAIN COMPLEXED WITH A POTENT SUBTYPE-SELECTIVE THYROMIMETIC

1n46, resolution 2.20Å

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