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| | ==Haddock model of mSIN3B PAH1 domain== | | ==Haddock model of mSIN3B PAH1 domain== |
| - | <StructureSection load='5y95' size='340' side='right' caption='[[5y95]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='5y95' size='340' side='right'caption='[[5y95]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5y95]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y95 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y95 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5y95]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y95 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8TL:propan-2-yl+(3R,6S,9aS)-3-ethyl-8-(3-methylbutyl)-6-(2-methylsulfanylethyl)-4,7-bis(oxidanylidene)-9,9a-dihydro-6H-pyrazino[2,1-c][1,2,4]oxadiazine-1-carboxylate'>8TL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cr7|2cr7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8TL:propan-2-yl+(3R,6S,9aS)-3-ethyl-8-(3-methylbutyl)-6-(2-methylsulfanylethyl)-4,7-bis(oxidanylidene)-9,9a-dihydro-6H-pyrazino[2,1-c][1,2,4]oxadiazine-1-carboxylate'>8TL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sin3b, Kiaa0700 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5y95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y95 OCA], [https://pdbe.org/5y95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y95 RCSB], [https://www.ebi.ac.uk/pdbsum/5y95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y95 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=5y95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y95 OCA], [http://pdbe.org/5y95 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y95 RCSB], [http://www.ebi.ac.uk/pdbsum/5y95 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y95 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SIN3B_MOUSE SIN3B_MOUSE]] Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription.<ref>PMID:7889570</ref> <ref>PMID:10620510</ref> | + | [https://www.uniprot.org/uniprot/SIN3B_MOUSE SIN3B_MOUSE] Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription.<ref>PMID:7889570</ref> <ref>PMID:10620510</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Hirao, Y]] | + | [[Category: Mus musculus]] |
| - | [[Category: Kurita, J]] | + | [[Category: Hirao Y]] |
| - | [[Category: Nishimura, Y]]
| + | [[Category: Kurita J]] |
| - | [[Category: Complex]] | + | [[Category: Nishimura Y]] |
| - | [[Category: Gene regulation]] | + | |
| - | [[Category: Haddock model]]
| + | |
| Structural highlights
Function
SIN3B_MOUSE Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription.[1] [2]
Publication Abstract from PubMed
The neuron-restrictive silencing factor NRSF/REST binds to neuron-restrictive silencing elements in neuronal genes and recruits corepressors such as mSin3 to inhibit epigenetically neuronal gene expression. Because dysregulation of NRSF/REST is related to neuropathic pain, here, we have designed compounds to target neuropathic pain based on the mSin3-binding helix structure of NRSF/REST and examined their ability to bind to mSin3 by NMR. One compound, mS-11, binds strongly to mSin3 with a binding mode similar to that of NRSF/REST. In a mouse model of neuropathic pain, mS-11 was found to ameliorate abnormal pain behavior and to reverse lost peripheral morphine analgesia. Furthermore, even in the less well epigenetically defined case of fibromyalgia, mS-11 ameliorated symptoms in a mouse model, suggesting that fibromyalgia is related to the dysfunction of NRSF/REST. Taken together, these findings show that the chemically optimized mimetic mS-11 can inhibit mSin3-NRSF/REST binding and successfully reverse lost peripheral and central morphine analgesia in mouse models of pain.
A mimetic of the mSin3-binding helix of NRSF/REST ameliorates abnormal pain behavior in chronic pain models.,Ueda H, Kurita JI, Neyama H, Hirao Y, Kouji H, Mishina T, Kasai M, Nakano H, Yoshimori A, Nishimura Y Bioorg Med Chem Lett. 2017 Oct 15;27(20):4705-4709. doi:, 10.1016/j.bmcl.2017.09.006. Epub 2017 Sep 7. PMID:28927787[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ayer DE, Lawrence QA, Eisenman RN. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell. 1995 Mar 10;80(5):767-76. PMID:7889570
- ↑ Yang Q, Kong Y, Rothermel B, Garry DJ, Bassel-Duby R, Williams RS. The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta) forms a co-repressor complex with mammalian sin3B. Biochem J. 2000 Jan 15;345 Pt 2:335-43. PMID:10620510
- ↑ Ueda H, Kurita JI, Neyama H, Hirao Y, Kouji H, Mishina T, Kasai M, Nakano H, Yoshimori A, Nishimura Y. A mimetic of the mSin3-binding helix of NRSF/REST ameliorates abnormal pain behavior in chronic pain models. Bioorg Med Chem Lett. 2017 Oct 15;27(20):4705-4709. doi:, 10.1016/j.bmcl.2017.09.006. Epub 2017 Sep 7. PMID:28927787 doi:http://dx.doi.org/10.1016/j.bmcl.2017.09.006
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