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4rzg

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Revision as of 10:35, 15 March 2023

Crystal Structure Analysis of the DNPA-bounded NUR77 Ligand binding Domain

Structural highlights

4rzg is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Harant H, Lindley IJ. Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Res. 2004 Oct 5;32(17):5280-90. Print 2004. PMID:15466594 doi:10.1093/nar/gkh856
↑ 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. Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation. Nat Chem Biol. 2015 May;11(5):339-46. doi: 10.1038/nchembio.1788. Epub 2015 Mar, 30. PMID:25822914 doi:http://dx.doi.org/10.1038/nchembio.1788

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rzg"

@@ Line 3: / Line 3: @@
 <StructureSection load='4rzg' size='340' side='right'caption='[[4rzg]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rzg]] 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=4RZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RZG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rzg]] 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=4RZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RZG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZHN:PENTYL+(3,5-DIHYDROXY-2-NONANOYLPHENYL)ACETATE'>ZHN</scene></td></tr>
+</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=ZHN:PENTYL+(3,5-DIHYDROXY-2-NONANOYLPHENYL)ACETATE'>ZHN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rze|4rze]], [[4rzf|4rzf]]</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=4rzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rzg OCA], [https://pdbe.org/4rzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rzg RCSB], [https://www.ebi.ac.uk/pdbsum/4rzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rzg ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GFRP1, HMR, NAK1, NR4A1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rzg OCA], [http://pdbe.org/4rzg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rzg RCSB], [http://www.ebi.ac.uk/pdbsum/4rzg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rzg ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chen, H]]
+[[Category: Chen H]]
-[[Category: Li, A]]
+[[Category: Li A]]
-[[Category: Li, F]]
+[[Category: Li F]]
-[[Category: Li, L]]
+[[Category: Li L]]
-[[Category: Lin, T]]
+[[Category: Lin T]]
-[[Category: Liu, Y]]
+[[Category: Liu Y]]
-[[Category: Tian, X]]
+[[Category: Tian X]]
-[[Category: Wu, Q]]
+[[Category: Wu Q]]
-[[Category: Nur77-lbd and dnpa complex]]
-[[Category: Transcription]]

4rzg

From Proteopedia

Revision as of 10:35, 15 March 2023

Crystal Structure Analysis of the DNPA-bounded NUR77 Ligand binding Domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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