View source for 3gyu


==Nuclear receptor DAF-12 from parasitic nematode Strongyloides stercoralis in complex with its physiological ligand dafachronic acid delta 7==
<StructureSection load='3gyu' size='340' side='right'caption='[[3gyu]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gyu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Strongyloides_stercoralis Strongyloides stercoralis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GYU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GYU 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DL7:(5BETA,14BETA,17ALPHA,25R)-3-OXOCHOLEST-7-EN-26-OIC+ACID'>DL7</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=3gyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gyu OCA], [https://pdbe.org/3gyu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gyu RCSB], [https://www.ebi.ac.uk/pdbsum/3gyu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gyu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9XZJ5_STRER Q9XZJ5_STRER] 
== 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/gy/3gyu_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3gyu ConSurf].
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== Publication Abstract from PubMed ==
Nematode parasitism is a worldwide health problem resulting in malnutrition and morbidity in over 1 billion people. The molecular mechanisms governing infection are poorly understood. Here, we report that an evolutionarily conserved nuclear hormone receptor signaling pathway governs development of the stage 3 infective larvae (iL3) in several nematode parasites, including Strongyloides stercoralis, Ancylostoma spp., and Necator americanus. As in the free-living Caenorhabditis elegans, steroid hormone-like dafachronic acids induced recovery of the dauer-like iL3 in parasitic nematodes by activating orthologs of the nuclear receptor DAF-12. Moreover, administration of dafachronic acid markedly reduced the pathogenic iL3 population in S. stercoralis, indicating the potential use of DAF-12 ligands to treat disseminated strongyloidiasis. To understand the pharmacology of targeting DAF-12, we solved the 3-dimensional structure of the S. stercoralis DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes.

Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes.,Wang Z, Zhou XE, Motola DL, Gao X, Suino-Powell K, Conneely A, Ogata C, Sharma KK, Auchus RJ, Lok JB, Hawdon JM, Kliewer SA, Xu HE, Mangelsdorf DJ Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9138-43. Epub 2009 Jun 2. PMID:19497877<ref>PMID:19497877</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 3gyu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Strongyloides stercoralis]]
[[Category: Auchus RJ]]
[[Category: Conneely A]]
[[Category: Kliewer SA]]
[[Category: Mangelsdorf DJ]]
[[Category: Motola DL]]
[[Category: Ogata C]]
[[Category: Sharma KK]]
[[Category: Suino-Powell K]]
[[Category: Wang Z]]
[[Category: Xu HE]]
[[Category: Zhou XE]]