This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3v3e

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal Structure of the Human Nur77 Ligand-binding Domain

Structural highlights

3v3e 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.
Method:	X-ray diffraction, Resolution 2.06Å
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

Liver kinase B1 (LKB1) has important roles in governing energy homeostasis by regulating the activity of the energy sensor kinase AMP-activated protein kinase (AMPK). The regulation of LKB1 function, however, is still poorly understood. Here we demonstrate that the orphan nuclear receptor Nur77 binds and sequesters LKB1 in the nucleus, thereby attenuating AMPK activation. This Nur77 function is antagonized by the chemical compound ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl]acetate (TMPA), which interacts with Nur77 with high affinity and at specific sites. TMPA binding of Nur77 results in the release and shuttling of LKB1 to the cytoplasm to phosphorylate AMPKalpha. Moreover, TMPA effectively reduces blood glucose and alleviates insulin resistance in type II db/db and high-fat diet- and streptozotocin-induced diabetic mice but not in diabetic littermates with the Nur77 gene knocked out. This study attains a mechanistic understanding of the regulation of LKB1-AMPK axis and implicates Nur77 as a new and amenable target for the design and development of therapeutics to treat metabolic diseases.

The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK.,Zhan YY, Chen Y, Zhang Q, Zhuang JJ, Tian M, Chen HZ, Zhang LR, Zhang HK, He JP, Wang WJ, Wu R, Wang Y, Shi C, Yang K, Li AZ, Xin YZ, Li TY, Yang JY, Zheng ZH, Yu CD, Lin SC, Chang C, Huang PQ, Lin T, Wu Q Nat Chem Biol. 2012 Nov;8(11):897-904. doi: 10.1038/nchembio.1069. Epub 2012 Sep , 16. PMID:22983157^[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
↑ Zhan YY, Chen Y, Zhang Q, Zhuang JJ, Tian M, Chen HZ, Zhang LR, Zhang HK, He JP, Wang WJ, Wu R, Wang Y, Shi C, Yang K, Li AZ, Xin YZ, Li TY, Yang JY, Zheng ZH, Yu CD, Lin SC, Chang C, Huang PQ, Lin T, Wu Q. The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nat Chem Biol. 2012 Nov;8(11):897-904. doi: 10.1038/nchembio.1069. Epub 2012 Sep , 16. PMID:22983157 doi:10.1038/nchembio.1069

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/3v3e"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Human Nur77 Ligand-binding Domain==
-<StructureSection load='3v3e' size='340' side='right' caption='[[3v3e]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+<StructureSection load='3v3e' size='340' side='right'caption='[[3v3e]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3v3e]] 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=3V3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V3E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3v3e]] 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=3V3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V3E 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></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]] 2.06&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v3q|3v3q]]</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></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR4A1, GFRP1, HMR, NAK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3v3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v3e OCA], [https://pdbe.org/3v3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v3e RCSB], [https://www.ebi.ac.uk/pdbsum/3v3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v3e ProSAT]</span></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=3v3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v3e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v3e RCSB], [http://www.ebi.ac.uk/pdbsum/3v3e PDBsum]</span></td></tr>
 </table>
+== Function ==
+[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 16: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3v3e" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 21: / Line 24: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Chen, Y]]
+[[Category: Large Structures]]
-[[Category: Lin, T]]
+[[Category: Chen Y]]
-[[Category: Shi, C]]
+[[Category: Lin T]]
-[[Category: Wu, Q]]
+[[Category: Shi C]]
-[[Category: Yang, K]]
+[[Category: Wu Q]]
-[[Category: Zhan, Y]]
+[[Category: Yang K]]
-[[Category: Zhang, Q]]
+[[Category: Zhan Y]]
-[[Category: Orphan nuclear receptor]]
+[[Category: Zhang Q]]
-[[Category: Transcription]]

3v3e

From Proteopedia

Current revision

Crystal Structure of the Human Nur77 Ligand-binding Domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox