7jtw
From Proteopedia
(Difference between revisions)
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==Crystal structure of RORgt with compound (4R)-6-[(2,5-dichloro-3-{[(2R,4R)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-yl]oxy}phenyl)amino]-6-oxo-4-phenylhexanoic acid== | ==Crystal structure of RORgt with compound (4R)-6-[(2,5-dichloro-3-{[(2R,4R)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-yl]oxy}phenyl)amino]-6-oxo-4-phenylhexanoic acid== | ||
| - | <StructureSection load='7jtw' size='340' side='right'caption='[[7jtw]]' scene=''> | + | <StructureSection load='7jtw' size='340' side='right'caption='[[7jtw]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JTW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7jtw]] is a 1 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=7JTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JTW FirstGlance]. <br> |
| - | </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=7jtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jtw OCA], [https://pdbe.org/7jtw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jtw RCSB], [https://www.ebi.ac.uk/pdbsum/7jtw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jtw ProSAT]</span></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]] 1.9Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VK4:(4R)-6-[(2,5-dichloro-3-{[(2R,4R)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-yl]oxy}phenyl)amino]-6-oxo-4-phenylhexanoic+acid'>VK4</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=7jtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jtw OCA], [https://pdbe.org/7jtw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jtw RCSB], [https://www.ebi.ac.uk/pdbsum/7jtw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jtw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat), which is a promising therapeutic target for immune diseases, is a major transcription factor of genes related to psoriasis pathogenesis, such as interleukin (IL)-17A, IL-22, and IL-23R. Inspired by the co-crystal structure of RORgammat, a 6-oxo-4-phenyl-hexanoic acid derivative 6a was designed, synthesized, and identified as a ligand of RORgammat. The structure-activity relationship (SAR) studies in 6a, which focus on the improvement of its membrane permeability profile by introducing chlorine atoms, led to finding 12a, which has a potent RORgammat inhibitory activity and a favorable pharmacokinetic profile. | ||
| + | |||
| + | Discovery of 6-Oxo-4-phenyl-hexanoic acid derivatives as RORgammat inverse agonists showing favorable ADME profile.,Nakajima R, Oono H, Kumazawa K, Ida T, Hirata J, White RD, Min X, Guzman-Perez A, Wang Z, Symons A, Singh SK, Mothe SR, Belyakov S, Chakrabarti A, Shuto S Bioorg Med Chem Lett. 2021 Mar 15;36:127786. doi: 10.1016/j.bmcl.2021.127786. , Epub 2021 Jan 23. PMID:33493627<ref>PMID:33493627</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7jtw" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Min X]] | [[Category: Min X]] | ||
[[Category: Wang Z]] | [[Category: Wang Z]] | ||
Current revision
Crystal structure of RORgt with compound (4R)-6-[(2,5-dichloro-3-{[(2R,4R)-1-(cyclopentanecarbonyl)-2-methylpiperidin-4-yl]oxy}phenyl)amino]-6-oxo-4-phenylhexanoic acid
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