6kkb: Difference between revisions
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==A novel agonist of THRb== | |||
<StructureSection load='6kkb' size='340' side='right'caption='[[6kkb]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6kkb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KKB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KKB FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8HO:2-[(1-methyl-4-oxidanyl-7-phenoxy-isoquinolin-3-yl)carbonylamino]ethanoic+acid'>8HO</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=6kkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kkb OCA], [http://pdbe.org/6kkb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kkb RCSB], [http://www.ebi.ac.uk/pdbsum/6kkb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kkb ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[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> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/THB_HUMAN THB_HUMAN]] High affinity receptor for triiodothyronine.<ref>PMID:17418816</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Nuclear receptors are important transcriptional factors that share high sequence identity and conserved domains, including a DNA-binding domain (DBD) and a ligand-binding domain (LBD). The LBD plays a crucial role in ligand-mediated nuclear receptor activity. Hundreds of different crystal structures of nuclear receptors have revealed a general mechanism for the molecular basis of ligand binding and ligand-mediated regulation of nuclear receptors. Despite the conserved fold of nuclear receptor LBDs, the ligand-binding pocket is the least conserved region among different nuclear receptor LBDs. Structural comparison and analysis show that several features of the pocket, like the size and also the shape, have contributed to the ligand binding affinity and specificity. In addition, the plastic nature of the ligand-binding pockets in many nuclear receptors provides greater flexibility to further accommodate specific ligands with a variety of conformations. Nuclear receptor coactivators usually contain multiple LXXLL motifs that are used to interact with nuclear receptors. The nuclear receptors respond differently to distinct ligands and readily exchange their ligands in different environments. The conformational flexibility of the AF-2 helix allows the nuclear receptor to sense the presence of the bound ligands, either an agonist or an antagonist, and to recruit the coactivators or corepressors that ultimately determine the transcriptional activation or repression of nuclear receptors. | |||
Structural and functional insights into nuclear receptor signaling.,Jin L, Li Y Adv Drug Deliv Rev. 2010 Oct 30;62(13):1218-26. doi: 10.1016/j.addr.2010.08.007. , Epub 2010 Aug 17. PMID:20723571<ref>PMID:20723571</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 6kkb" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Li, Y]] | [[Category: Li, Y]] | ||
[[Category: Yao, B Q]] | |||
[[Category: Agonist]] | |||
[[Category: Anemia]] | |||
[[Category: Thyroid hormone receptor]] | |||
[[Category: Transcription]] | |||