3up3

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==Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-cholestenoic acid==
==Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-cholestenoic acid==
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<StructureSection load='3up3' size='340' side='right' caption='[[3up3]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
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<StructureSection load='3up3' size='340' side='right'caption='[[3up3]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3up3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ancylostoma_ceylanicum Ancylostoma ceylanicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UP3 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3up3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ancylostoma_ceylanicum Ancylostoma ceylanicum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UP3 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XCA:(8ALPHA,10ALPHA,25S)-3-HYDROXYCHOLESTA-3,5-DIEN-26-OIC+ACID'>XCA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3up0|3up0]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=XCA:(8ALPHA,10ALPHA,25S)-3-HYDROXYCHOLESTA-3,5-DIEN-26-OIC+ACID'>XCA</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">daf-12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=53326 Ancylostoma ceylanicum])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3up3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3up3 OCA], [https://pdbe.org/3up3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3up3 RCSB], [https://www.ebi.ac.uk/pdbsum/3up3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3up3 ProSAT]</span></td></tr>
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<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=3up3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3up3 OCA], [http://pdbe.org/3up3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3up3 RCSB], [http://www.ebi.ac.uk/pdbsum/3up3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3up3 ProSAT]</span></td></tr>
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</table>
</table>
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== Disease ==
 
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[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
 
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
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[https://www.uniprot.org/uniprot/H0USY8_9BILA H0USY8_9BILA]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bile acid-like molecules named dafachronic acids (DAs) control the dauer formation program in C. elegans through the nuclear receptor DAF-12. This mechanism is conserved in parasitic nematodes to regulate their dauer-like infective larvae stage and as such the DAF-12 ligand binding domain (LBD) has been identified as an important therapeutic target in human parasitic hookworm species that infect more than 600 million people worldwide. Here, we report two X-ray crystal structures of the hookworm Ancylostoma ceylanicum DAF-12 LBD in complex with DA and cholestenoic acid (a bile acid-like metabolite), respectively. Structure analysis and functional studies reveal key residues responsible for species-specific ligand responses of DAF-12. Furthermore, DA binds to DAF-12 mechanistically and structurally similar to bile acids binding to the mammalian bile acid receptor FXR. Activation of DAF-12 by cholestenoic acid and the cholestenoic acid complex structure suggest that bile acid-like signaling pathways have been conserved in nematodes and mammals. Together, these results reveal the molecular mechanism for the interplay between parasite and host, provide a structural framework for DAF-12 as a promising target in treating nematode parasitism, and provide insight into the evolution of gut parasite hormone signaling pathways.
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Structural conservation of ligand binding reveals a bile acid-like signaling pathway in nematodes.,Zhi X, Zhou XE, Melcher K, Motola DL, Gelmedin V, Hawdon J, Kliewer SA, Mangelsdorf DJ, Xu HE J Biol Chem. 2011 Dec 21. PMID:22170062<ref>PMID:22170062</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3up3" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Ancylostoma ceylanicum]]
[[Category: Ancylostoma ceylanicum]]
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[[Category: Gelmedin, V]]
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[[Category: Homo sapiens]]
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[[Category: Hawdon, J]]
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[[Category: Large Structures]]
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[[Category: Kliewer, S A]]
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[[Category: Gelmedin V]]
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[[Category: Mangelsdorf, D J]]
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[[Category: Hawdon J]]
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[[Category: Melcher, K]]
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[[Category: Kliewer SA]]
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[[Category: Motola, D L]]
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[[Category: Mangelsdorf DJ]]
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[[Category: Xu, H E]]
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[[Category: Melcher K]]
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[[Category: Zhi, X]]
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[[Category: Motola DL]]
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[[Category: Zhou, X E]]
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[[Category: Xu HE]]
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[[Category: Ligand binding domain]]
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[[Category: Zhi X]]
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[[Category: Nematode]]
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[[Category: Zhou XE]]
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[[Category: Steroid binding protein-transcription complex]]
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Current revision

Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-cholestenoic acid

PDB ID 3up3

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