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5T4R

NMR solution structure of the Nav1.7 selective spider venom-derived peptide Pn3a

5T4R の概要
エントリーDOI10.2210/pdb5t4r/pdb
NMR情報BMRB: 30164
分子名称Mu-theraphotoxin-Pn3a (1 entity in total)
機能のキーワードtarantula peptide toxin, inhibitor cystine knot, voltage-gated sodium channel modifier, voltage sensor modifier, toxin
由来する生物種Theraphosidae (tarantulas)
タンパク質・核酸の鎖数1
化学式量合計4285.99
構造登録者
Rosengren, K.J.,Armstrong, D.A.,Vetter, I. (登録日: 2016-08-30, 公開日: 2017-09-06, 最終更新日: 2024-11-13)
主引用文献Deuis, J.R.,Dekan, Z.,Wingerd, J.S.,Smith, J.J.,Munasinghe, N.R.,Bhola, R.F.,Imlach, W.L.,Herzig, V.,Armstrong, D.A.,Rosengren, K.J.,Bosmans, F.,Waxman, S.G.,Dib-Hajj, S.D.,Escoubas, P.,Minett, M.S.,Christie, M.J.,King, G.F.,Alewood, P.F.,Lewis, R.J.,Wood, J.N.,Vetter, I.
Pharmacological characterisation of the highly Na V 1.7 selective spider venom peptide Pn3a.
Sci Rep, 7:40883-40883, 2017
Cited by
PubMed Abstract: Human genetic studies have implicated the voltage-gated sodium channel Na1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na1.7 (IC 0.9 nM) with at least 40-1000-fold selectivity over all other Na subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na1.7 inhibitors produced profound analgesia. Our results suggest that in these inflammatory models, acute administration of peripherally restricted Na1.7 inhibitors can only produce analgesia when administered in combination with an opioid.
PubMed: 28106092
DOI: 10.1038/srep40883
主引用文献が同じPDBエントリー
実験手法
SOLUTION NMR
構造検証レポート
Validation report summary of 5t4r
検証レポート(詳細版)ダウンロードをダウンロード

227561

件を2024-11-20に公開中

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