4ymq
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ymq]] 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=4YMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YMQ FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ymq]] 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=4YMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YMQ FirstGlance]. <br> | ||
| - | </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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZBD:4-{3-[4-(1,1,1,3,3,3-HEXAFLUORO-2-HYDROXYPROPAN-2-YL)BENZYL]-2,2-DIOXIDO-2,1,3-BENZOTHIADIAZOL-1(3H)-YL}-N-[(2R)-4-HYDROXYBUTAN-2-YL]-N-METHYLBUTANAMIDE'>ZBD</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]] 2Å</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZBD:4-{3-[4-(1,1,1,3,3,3-HEXAFLUORO-2-HYDROXYPROPAN-2-YL)BENZYL]-2,2-DIOXIDO-2,1,3-BENZOTHIADIAZOL-1(3H)-YL}-N-[(2R)-4-HYDROXYBUTAN-2-YL]-N-METHYLBUTANAMIDE'>ZBD</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=4ymq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ymq OCA], [https://pdbe.org/4ymq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ymq RCSB], [https://www.ebi.ac.uk/pdbsum/4ymq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ymq 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=4ymq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ymq OCA], [https://pdbe.org/4ymq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ymq RCSB], [https://www.ebi.ac.uk/pdbsum/4ymq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ymq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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. | [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 == | ||
| - | Structure-based and pharmacophore-based virtual screening in combination with combinatorial chemistry and X-ray crystallography led to the discovery of a new class of benzothiadiazole dioxide analogs with functional activity as RORC inverse agonists. The early RORC SAR compound 14 exhibited RORC inhibition in a cell based reporter gene assay of 5.7muM and bound to RORC with an affinity of 1.6muM in a fluorescence polarization assay displacing a ligand binding site probe. Crystallography confirmed the binding mode of the compound in the ligand binding domain displaying the engagement of a novel sub pocket close to Ser404. Subsequent optimization yielded compounds with enhanced RORC inverse agonist activity. The most active compound 19 showed an IC50 of 440nM in a human PBMC assay. | ||
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| - | Discovery of 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide analogs as new RORC modulators.,Muegge I, Collin D, Cook B, Hill-Drzewi M, Horan J, Kugler S, Labadia M, Li X, Smith L, Zhang Y Bioorg Med Chem Lett. 2015 Mar 23. pii: S0960-894X(15)00248-6. doi:, 10.1016/j.bmcl.2015.03.042. PMID:25840886<ref>PMID:25840886</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4ymq" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
X-ray co-structure of nuclear receptor ROR-GAMMAT + SRC2 peptide with a benzothiadiazole dioxide inverse agonist
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