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| | ==Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-delta7-dafachronic acid== | | ==Nuclear receptor DAF-12 from hookworm Ancylostoma ceylanicum in complex with (25S)-delta7-dafachronic acid== |
| - | <StructureSection load='3up0' size='340' side='right' caption='[[3up0]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3up0' size='340' side='right'caption='[[3up0]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3up0]] is a 4 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=3UP0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UP0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3up0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ancylostoma_ceylanicum Ancylostoma ceylanicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UP0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D7S:(5BETA,14BETA,17ALPHA,25S)-3-OXOCHOLEST-7-EN-26-OIC+ACID'>D7S</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D7S:(5BETA,14BETA,17ALPHA,25S)-3-OXOCHOLEST-7-EN-26-OIC+ACID'>D7S</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3up3|3up3]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3up3|3up3]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">daf-12 ([https://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=3up0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3up0 OCA], [http://pdbe.org/3up0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3up0 RCSB], [http://www.ebi.ac.uk/pdbsum/3up0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3up0 ProSAT]</span></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=3up0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3up0 OCA], [https://pdbe.org/3up0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3up0 RCSB], [https://www.ebi.ac.uk/pdbsum/3up0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3up0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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. | + | [[https://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 == |
| - | [[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> | + | [[https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Ancylostoma ceylanicum]] | | [[Category: Ancylostoma ceylanicum]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Gelmedin, V]] | | [[Category: Gelmedin, V]] |
| | [[Category: Hawdon, J]] | | [[Category: Hawdon, J]] |
| Structural highlights
Disease
[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
[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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J. 1998 Jan 15;17(2):507-19. PMID:9430642 doi:10.1093/emboj/17.2.507
- ↑ Zhi X, Zhou XE, Melcher K, Motola DL, Gelmedin V, Hawdon J, Kliewer SA, Mangelsdorf DJ, Xu HE. Structural conservation of ligand binding reveals a bile acid-like signaling pathway in nematodes. J Biol Chem. 2011 Dec 21. PMID:22170062 doi:10.1074/jbc.M111.315242
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