View source for 1xnn


==CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH (3A-ALPHA-,4-ALPHA 7-ALPHA-,7A-ALPHA-)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE.==
<StructureSection load='1xnn' size='340' side='right'caption='[[1xnn]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xnn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XNN FirstGlance]. <br>
</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>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYQ:REL-(3AR,4S,7R,7AS)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE'>HYQ</scene></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=1xnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xnn OCA], [https://pdbe.org/1xnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xnn RCSB], [https://www.ebi.ac.uk/pdbsum/1xnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xnn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ANDR_RAT ANDR_RAT] Note=Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).<ref>PMID:2341409</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ANDR_RAT ANDR_RAT] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3 (By similarity).<ref>PMID:17181141</ref> <ref>PMID:17008401</ref> 
== 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/xn/1xnn_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=1xnn ConSurf].
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== Publication Abstract from PubMed ==
A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). Co-crystallization of members of this family of inhibitors was successfully accomplished with the T877A AR LBD. A working model of how this class of compounds functions to antagonize the AR was created. Based on this model, it was proposed that expanding the bicyclic portion of the molecule should result in analogs which function as effective antagonists against a variety of AR isoforms. In contrast to what was predicted by the model, SAR around this new series was dictated by the aniline portion rather than the bicyclic portion of the molecule.

Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists.,Salvati ME, Balog A, Shan W, Wei DD, Pickering D, Attar RM, Geng J, Rizzo CA, Gottardis MM, Weinmann R, Krystek SR, Sack J, An Y, Kish K Bioorg Med Chem Lett. 2005 Jan 17;15(2):271-6. PMID:15603938<ref>PMID:15603938</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1xnn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Androgen receptor 3D structures|Androgen receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Sack J]]