3up3
From Proteopedia
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| - | + | ==Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-cholestenoic acid== | |
| - | + | <StructureSection load='3up3' size='340' side='right' caption='[[3up3]], [[Resolution|resolution]] 1.25Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <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> | |
| - | ==Disease== | + | </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> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3up0|3up0]]</td></tr> | ||
| + | <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> | ||
| + | <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://www.rcsb.org/pdb/explore.do?structureId=3up3 RCSB], [http://www.ebi.ac.uk/pdbsum/3up3 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[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. | [[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 == | ||
| + | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Ancylostoma ceylanicum]] | [[Category: Ancylostoma ceylanicum]] | ||
| - | [[Category: Gelmedin, V | + | [[Category: Gelmedin, V]] |
| - | [[Category: Hawdon, J | + | [[Category: Hawdon, J]] |
| - | [[Category: Kliewer, S A | + | [[Category: Kliewer, S A]] |
| - | [[Category: Mangelsdorf, D J | + | [[Category: Mangelsdorf, D J]] |
| - | [[Category: Melcher, K | + | [[Category: Melcher, K]] |
| - | [[Category: Motola, D L | + | [[Category: Motola, D L]] |
| - | [[Category: Xu, H E | + | [[Category: Xu, H E]] |
| - | [[Category: Zhi, X | + | [[Category: Zhi, X]] |
| - | [[Category: Zhou, X E | + | [[Category: Zhou, X E]] |
[[Category: Ligand binding domain]] | [[Category: Ligand binding domain]] | ||
[[Category: Nematode]] | [[Category: Nematode]] | ||
[[Category: Steroid binding protein-transcription complex]] | [[Category: Steroid binding protein-transcription complex]] | ||
Revision as of 06:36, 21 December 2014
Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-cholestenoic acid
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