EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Ligand activation mechanisms of human KCNQ2 channel.
ジャーナル・号・ページ	Nat Commun, Vol. 14, Issue 1, Page 6632, Year 2023
掲載日	2023年10月19日
著者	Demin Ma / Yueming Zheng / Xiaoxiao Li / Xiaoyu Zhou / Zhenni Yang / Yan Zhang / Long Wang / Wenbo Zhang / Jiajia Fang / Guohua Zhao / Panpan Hou / Fajun Nan / Wei Yang / Nannan Su / Zhaobing Gao / Jiangtao Guo /
PubMed 要旨	The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but ...The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2.
リンク	Nat Commun / PubMed:37857637 / PubMed Central
手法	EM (単粒子)
解像度	2.5 - 3.5 Å
構造データ	35877 8izy EMDB-35877, PDB-8izy: Human KCNQ2-CaM in complex with HN37 手法: EM (単粒子) / 解像度: 2.5 Å 35879 8j00 EMDB-35879, PDB-8j00: Human KCNQ2-CaM in complex with CBD 手法: EM (単粒子) / 解像度: 3.0 Å 35880 8j01 EMDB-35880, PDB-8j01: Human KCNQ2-CaM in complex with CBD and PIP2 手法: EM (単粒子) / 解像度: 3.1 Å 35881 8j02 EMDB-35881, PDB-8j02: Human KCNQ2(F104A)-CaM-PIP2-CBD complex in state II 手法: EM (単粒子) / 解像度: 3.5 Å 35882 8j03 EMDB-35882, PDB-8j03: Human KCNQ2(F104A)-CaM-PIP2-CBD complex in state I 手法: EM (単粒子) / 解像度: 2.7 Å 35883 8j04 EMDB-35883, PDB-8j04: Human KCNQ2-CaM-HN37 complex in the presence of PIP2 手法: EM (単粒子) / 解像度: 2.7 Å 35884 8j05 EMDB-35884, PDB-8j05: Human KCNQ2-CaM complex in the presence of PIP2 手法: EM (単粒子) / 解像度: 2.7 Å 37270 8w4u EMDB-37270, PDB-8w4u: human KCNQ2-CaM in complex with PIP2 and HN37 手法: EM (単粒子) / 解像度: 3.3 Å
化合物	ChemComp-9MF: methyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynyl-amino]-2,6-dimethyl-phenyl]carbamate ChemComp-P0T: cannabidiol / カンナビジオ-ル / カンナビジオール ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate / 1-O-(1-O,2-O-ジオクタノイル-L-グリセロ-3-ホスホ)-D-myo-イノシト-ル4,5-ビスりん酸
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / potassium voltage-gated channel / HN37 / CBD / PIP2 (ホスファチジルイノシトール4,5-ビスリン酸)