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4rzf

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==Crystal Structure Analysis of the NUR77 Ligand Binding Domain, S441W mutant==
==Crystal Structure Analysis of the NUR77 Ligand Binding Domain, S441W mutant==
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<StructureSection load='4rzf' size='340' side='right' caption='[[4rzf]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
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<StructureSection load='4rzf' size='340' side='right'caption='[[4rzf]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4rzf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RZF FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4rzf]] 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=4RZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RZF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rze|4rze]], [[4rzg|4rzg]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<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=4rzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rzf OCA], [http://pdbe.org/4rzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rzf RCSB], [http://www.ebi.ac.uk/pdbsum/4rzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rzf ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rzf OCA], [https://pdbe.org/4rzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rzf RCSB], [https://www.ebi.ac.uk/pdbsum/4rzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rzf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/NR4A1_HUMAN NR4A1_HUMAN]] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.<ref>PMID:15466594</ref>
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[https://www.uniprot.org/uniprot/NR4A1_HUMAN NR4A1_HUMAN] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.<ref>PMID:15466594</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor Nur77 (also known as TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-kappaB activity and suppressing aberrant cytokine production. Nur77 directly associates with p65 to block its binding to the kappaB element. However, this function of Nur77 is countered by the LPS-activated p38alpha phosphorylation of Nur77. Dampening the interaction between Nur77 and p38alpha would favor Nur77 suppression of the hyperinflammatory response. A compound, n-pentyl 2-[3,5-dihydroxy-2-(1-nonanoyl) phenyl]acetate, screened from a Nur77-biased library, blocked the Nur77-p38alpha interaction by targeting the ligand-binding domain of Nur77 and restored the suppression of the hyperinflammatory response through Nur77 inhibition of NF-kappaB. This study associates the nuclear receptor with immune homeostasis and implicates a new therapeutic strategy to treat hyperinflammatory responses by targeting a p38alpha substrate to modulate p38alpha-regulated functions.
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Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation.,Li L, Liu Y, Chen HZ, Li FW, Wu JF, Zhang HK, He JP, Xing YZ, Chen Y, Wang WJ, Tian XY, Li AZ, Zhang Q, Huang PQ, Han J, Lin T, Wu Q Nat Chem Biol. 2015 May;11(5):339-46. doi: 10.1038/nchembio.1788. Epub 2015 Mar, 30. PMID:25822914<ref>PMID:25822914</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4rzf" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Chen, H]]
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[[Category: Homo sapiens]]
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[[Category: Li, A]]
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[[Category: Large Structures]]
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[[Category: Li, F]]
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[[Category: Chen H]]
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[[Category: Li, L]]
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[[Category: Li A]]
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[[Category: Lin, T]]
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[[Category: Li F]]
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[[Category: Liu, Y]]
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[[Category: Li L]]
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[[Category: Tian, X]]
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[[Category: Lin T]]
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[[Category: Wu, Q]]
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[[Category: Liu Y]]
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[[Category: Transcription]]
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[[Category: Tian X]]
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[[Category: Wu Q]]

Current revision

Crystal Structure Analysis of the NUR77 Ligand Binding Domain, S441W mutant

PDB ID 4rzf

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