3b0w

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[[Image:3b0w.png|left|200px]]
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==Crystal structure of the orphan nuclear receptor ROR(gamma)t ligand-binding domain in complex with digoxin==
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<StructureSection load='3b0w' size='340' side='right' caption='[[3b0w]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3b0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3B0W FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGX:DIGOXIN'>DGX</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RORC, NR1F3, RORG, RZRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3b0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3b0w RCSB], [http://www.ebi.ac.uk/pdbsum/3b0w PDBsum]</span></td></tr>
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<table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The retinoic acid-related orphan nuclear receptor gammat (RORgammat)/RORgamma2 is well known as a master regulator of interleukin 17 (IL-17)-producing helper T (Th17) cell development. To develop a therapeutic agent against Th17-mediated autoimmune diseases, we screened chemical compounds and successfully found that digoxin inhibited IL-17 production. Further studies revealed that digoxin bound to the ligand binding domain of RORgammat and suppressed Th17 differentiation without affecting Th1 differentiation. To better understand the structural basis for the inhibitory activity of digoxin, we determined the crystal structure of the RORgammat ligand-binding domain in complex with digoxin at 2.2 A resolution. The structure reveals that digoxin binds to the ligand-binding pocket protruding between helices H3 and H11 from the pocket. In addition, digoxin disrupts the key interaction important for the agonistic activity, resulting in preventing the positioning of helix H12 in the active conformation, thus antagonizing coactivator interaction. Functional studies demonstrated that digoxin inhibited RORgammat activity and decreased IL-17 production but not RORalpha activity. Digoxin inhibited IL-17 production in CD4(+) T cells from experimental autoimmune encephalomyelitis mice. Our data indicates that RORgammat is a promising therapeutic target for Th17-derived autoimmune diseases and our structural data will help to design novel RORgammat antagonists.
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Structural Basis of Digoxin That Antagonizes ROR{gamma}t Receptor Activity and Suppresses Th17 Cell Differentiation and Interleukin (IL)-17 Production.,Fujita-Sato S, Ito S, Isobe T, Ohyama T, Wakabayashi K, Morishita K, Ando O, Isono F J Biol Chem. 2011 Sep 9;286(36):31409-17. Epub 2011 Jul 6. PMID:21733845<ref>PMID:21733845</ref>
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The line below this paragraph, containing "STRUCTURE_3b0w", creates the "Structure Box" on the page.
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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or leave the SCENE parameter empty for the default display.
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{{STRUCTURE_3b0w| PDB=3b0w | SCENE= }}
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===Crystal structure of the orphan nuclear receptor ROR(gamma)t ligand-binding domain in complex with digoxin===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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The line below this paragraph, {{ABSTRACT_PUBMED_21733845}}, adds the Publication Abstract to the page
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__TOC__
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(as it appears on PubMed at http://www.pubmed.gov), where 21733845 is the PubMed ID number.
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</StructureSection>
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{{ABSTRACT_PUBMED_21733845}}
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==About this Structure==
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[[3b0w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B0W OCA].
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==Reference==
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<ref group="xtra">PMID:021733845</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ando, O.]]
[[Category: Ando, O.]]

Revision as of 11:07, 14 May 2014

Crystal structure of the orphan nuclear receptor ROR(gamma)t ligand-binding domain in complex with digoxin

3b0w, resolution 2.20Å

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