4jgv: Difference between revisions
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==Crystal Structure of Human Nur77 Ligand-binding Domain in Complex with THPN== | |||
<StructureSection load='4jgv' size='340' side='right' caption='[[4jgv]], [[Resolution|resolution]] 3.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jgv]] 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=4JGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JGV FirstGlance]. <br> | |||
==Function== | </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=T94:1-(3,4,5-TRIHYDROXYPHENYL)NONAN-1-ONE'>T94</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kzi|4kzi]], [[4kzj|4kzj]], [[4kzm|4kzm]]</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 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=4jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jgv RCSB], [http://www.ebi.ac.uk/pdbsum/4jgv PDBsum]</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> | [[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> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds. The autophagic cascade comprises TR3 translocation to mitochondria through interaction with the mitochondrial outer membrane protein Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70 channel proteins, dissipation of mitochondrial membrane potential by the permeability transition pore complex ANT1-VDAC1 and induction of autophagy. This process leads to excessive mitochondria clearance and irreversible cell death. It implicates a new approach to melanoma therapy through activation of a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death. | |||
Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.,Wang WJ, Wang Y, Chen HZ, Xing YZ, Li FW, Zhang Q, Zhou B, Zhang HK, Zhang J, Bian XL, Li L, Liu Y, Zhao BX, Chen Y, Wu R, Li AZ, Yao LM, Chen P, Zhang Y, Tian XY, Beermann F, Wu M, Han J, Huang PQ, Lin T, Wu Q Nat Chem Biol. 2014 Feb;10(2):133-40. doi: 10.1038/nchembio.1406. Epub 2013 Dec, 8. PMID:24316735<ref>PMID:24316735</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: Chen, H | == References == | ||
[[Category: Li, A | <references/> | ||
[[Category: Li, F | __TOC__ | ||
[[Category: Lin, T | </StructureSection> | ||
[[Category: Tian, X | [[Category: Human]] | ||
[[Category: Wan, W | [[Category: Chen, H]] | ||
[[Category: Wan, Y | [[Category: Li, A]] | ||
[[Category: Wu, Q | [[Category: Li, F]] | ||
[[Category: Xing, Y | [[Category: Lin, T]] | ||
[[Category: Zhang, Q | [[Category: Tian, X]] | ||
[[Category: Wan, W]] | |||
[[Category: Wan, Y]] | |||
[[Category: Wu, Q]] | |||
[[Category: Xing, Y]] | |||
[[Category: Zhang, Q]] | |||
[[Category: Transcription]] | [[Category: Transcription]] | ||
Revision as of 20:58, 24 December 2014
Crystal Structure of Human Nur77 Ligand-binding Domain in Complex with THPNCrystal Structure of Human Nur77 Ligand-binding Domain in Complex with THPN
Structural highlights
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 PubMedAutophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds. The autophagic cascade comprises TR3 translocation to mitochondria through interaction with the mitochondrial outer membrane protein Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70 channel proteins, dissipation of mitochondrial membrane potential by the permeability transition pore complex ANT1-VDAC1 and induction of autophagy. This process leads to excessive mitochondria clearance and irreversible cell death. It implicates a new approach to melanoma therapy through activation of a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.,Wang WJ, Wang Y, Chen HZ, Xing YZ, Li FW, Zhang Q, Zhou B, Zhang HK, Zhang J, Bian XL, Li L, Liu Y, Zhao BX, Chen Y, Wu R, Li AZ, Yao LM, Chen P, Zhang Y, Tian XY, Beermann F, Wu M, Han J, Huang PQ, Lin T, Wu Q Nat Chem Biol. 2014 Feb;10(2):133-40. doi: 10.1038/nchembio.1406. Epub 2013 Dec, 8. PMID:24316735[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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