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| | ==Crystal structure of the ligand binding domain of RORC with T0901317== | | ==Crystal structure of the ligand binding domain of RORC with T0901317== |
| - | <StructureSection load='4nb6' size='340' side='right' caption='[[4nb6]], [[Resolution|resolution]] 2.85Å' scene=''> | + | <StructureSection load='4nb6' size='340' side='right'caption='[[4nb6]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nb6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NB6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NB6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nb6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NB6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=444:N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE'>444</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pqc|1pqc]], [[1pq9|1pq9]], [[2o91|2o91]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=444:N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE'>444</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1F3, RORC, RORG, RZRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4nb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nb6 OCA], [https://pdbe.org/4nb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nb6 RCSB], [https://www.ebi.ac.uk/pdbsum/4nb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nb6 ProSAT]</span></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=4nb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nb6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nb6 RCSB], [http://www.ebi.ac.uk/pdbsum/4nb6 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. | + | [https://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4nb6" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hymowitz, S G]] | + | [[Category: Large Structures]] |
| - | [[Category: Leon, G Boenig-de]] | + | [[Category: Boenig-de Leon G]] |
| - | [[Category: Alpha-helical]] | + | [[Category: Hymowitz SG]] |
| - | [[Category: Nucleus]]
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| - | [[Category: Transcription]]
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| - | [[Category: Transcription factor]]
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| Structural highlights
Function
RORG_HUMAN Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
Publication Abstract from PubMed
The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.
Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc.,Fauber BP, de Leon Boenig G, Burton B, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, Liimatta M, Lockey P, Norman M, Ouyang W, Rene O, Wong H Bioorg Med Chem Lett. 2013 Dec 15;23(24):6604-9. doi: 10.1016/j.bmcl.2013.10.054., Epub 2013 Nov 4. PMID:24239186[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fauber BP, de Leon Boenig G, Burton B, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, Liimatta M, Lockey P, Norman M, Ouyang W, Rene O, Wong H. Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6604-9. doi: 10.1016/j.bmcl.2013.10.054., Epub 2013 Nov 4. PMID:24239186 doi:http://dx.doi.org/10.1016/j.bmcl.2013.10.054
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