View source for 1xc5


==Solution Structure of the SMRT Deacetylase Activation Domain==
<StructureSection load='1xc5' size='340' side='right'caption='[[1xc5]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xc5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XC5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1xc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xc5 OCA], [https://pdbe.org/1xc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xc5 RCSB], [https://www.ebi.ac.uk/pdbsum/1xc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xc5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NCOR2_HUMAN NCOR2_HUMAN] Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xc/1xc5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1xc5 ConSurf].
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== Publication Abstract from PubMed ==
SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that play an essential role in the regulation of development and metabolism. This role is achieved, in part, through the recruitment of a key histone deacetylase (HDAC3), which is itself indispensable for cell viability. The assembly of HDAC3 with the deacetylase activation domain (DAD) of SMRT and NCoR is required for activation of the otherwise inert deacetylase. The DAD comprises an N-terminal DAD-specific motif and a C-terminal SANT (SWI3/ADA2/NCoR/TFIIIB)-like domain. We report here the solution structure of the DAD from SMRT, which reveals a four-helical structure. The DAD differs from the SANT (and MYB) domains in that (i) it has an additional N-terminal helix and (ii) there is a notable hydrophobic groove on the surface of the domain. Structure-guided mutagenesis, combined with interaction assays, showed that residues in the vicinity of the hydrophobic groove are required for interaction with (and hence activation of) HDAC3. Importantly, one surface-exposed lysine is required for activation of HDAC3, but not for interaction. This lysine may play a uniquely important role in the mechanism of activating HDAC3.

Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors.,Codina A, Love JD, Li Y, Lazar MA, Neuhaus D, Schwabe JW Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6009-14. Epub 2005 Apr 18. PMID:15837933<ref>PMID:15837933</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Nuclear receptor corepressor|Nuclear receptor corepressor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Codina A]]
[[Category: Lazar MA]]
[[Category: Li Y]]
[[Category: Love JD]]
[[Category: Neuhaus D]]
[[Category: Schwabe JWR]]