5Y95
Haddock model of mSIN3B PAH1 domain
Summary for 5Y95
| Entry DOI | 10.2210/pdb5y95/pdb |
| Related | 2CR7 |
| NMR Information | BMRB: 27227 |
| Descriptor | Paired amphipathic helix protein Sin3b, 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 (2 entities in total) |
| Functional Keywords | haddock model, complex, gene regulation |
| Biological source | Mus musculus (Mouse) |
| Cellular location | Nucleus : Q62141 |
| Total number of polymer chains | 1 |
| Total formula weight | 9079.18 |
| Authors | Kurita, J.,Hirao, Y.,Nishimura, Y. (deposition date: 2017-08-22, release date: 2017-10-04, Last modification date: 2025-03-12) |
| Primary citation | Ueda, H.,Kurita, J.I.,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., 27:4705-4709, 2017 Cited by PubMed Abstract: 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. PubMed: 28927787DOI: 10.1016/j.bmcl.2017.09.006 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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