A structural atlas of druggable sites on Nav channels
Voltage-gated sodium (Nav) channels govern membrane excitability by initiating and propagating action potentials. Consistent with their physiological significance, dysfunction, or mutations in these channels are associated with various channelopathies. Nav channels are thereby major targets for vari...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Channels |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19336950.2023.2287832 |
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| author | Zhangqiang Li Qiurong Wu Nieng Yan |
| author_facet | Zhangqiang Li Qiurong Wu Nieng Yan |
| author_sort | Zhangqiang Li |
| collection | DOAJ |
| description | Voltage-gated sodium (Nav) channels govern membrane excitability by initiating and propagating action potentials. Consistent with their physiological significance, dysfunction, or mutations in these channels are associated with various channelopathies. Nav channels are thereby major targets for various clinical and investigational drugs. In addition, a large number of natural toxins, both small molecules and peptides, can bind to Nav channels and modulate their functions. Technological breakthrough in cryo-electron microscopy (cryo-EM) has enabled the determination of high-resolution structures of eukaryotic and eventually human Nav channels, alone or in complex with auxiliary subunits, toxins, and drugs. These studies have not only advanced our comprehension of channel architecture and working mechanisms but also afforded unprecedented clarity to the molecular basis for the binding and mechanism of action (MOA) of prototypical drugs and toxins. In this review, we will provide an overview of the recent advances in structural pharmacology of Nav channels, encompassing the structural map for ligand binding on Nav channels. These findings have established a vital groundwork for future drug development. |
| format | Article |
| id | doaj-art-5652f4a817e64dfeb2bfebf45b42f072 |
| institution | Kabale University |
| issn | 1933-6950 1933-6969 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Channels |
| spelling | doaj-art-5652f4a817e64dfeb2bfebf45b42f0722024-12-09T07:27:27ZengTaylor & Francis GroupChannels1933-69501933-69692024-12-0118110.1080/19336950.2023.2287832A structural atlas of druggable sites on Nav channelsZhangqiang Li0Qiurong Wu1Nieng Yan2Beijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, ChinaBeijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, ChinaBeijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, ChinaVoltage-gated sodium (Nav) channels govern membrane excitability by initiating and propagating action potentials. Consistent with their physiological significance, dysfunction, or mutations in these channels are associated with various channelopathies. Nav channels are thereby major targets for various clinical and investigational drugs. In addition, a large number of natural toxins, both small molecules and peptides, can bind to Nav channels and modulate their functions. Technological breakthrough in cryo-electron microscopy (cryo-EM) has enabled the determination of high-resolution structures of eukaryotic and eventually human Nav channels, alone or in complex with auxiliary subunits, toxins, and drugs. These studies have not only advanced our comprehension of channel architecture and working mechanisms but also afforded unprecedented clarity to the molecular basis for the binding and mechanism of action (MOA) of prototypical drugs and toxins. In this review, we will provide an overview of the recent advances in structural pharmacology of Nav channels, encompassing the structural map for ligand binding on Nav channels. These findings have established a vital groundwork for future drug development.https://www.tandfonline.com/doi/10.1080/19336950.2023.2287832Nav channelsstructural pharmacologymode of action (MOA)analgesicsanti-epilepsy drugs (AED) |
| spellingShingle | Zhangqiang Li Qiurong Wu Nieng Yan A structural atlas of druggable sites on Nav channels Channels Nav channels structural pharmacology mode of action (MOA) analgesics anti-epilepsy drugs (AED) |
| title | A structural atlas of druggable sites on Nav channels |
| title_full | A structural atlas of druggable sites on Nav channels |
| title_fullStr | A structural atlas of druggable sites on Nav channels |
| title_full_unstemmed | A structural atlas of druggable sites on Nav channels |
| title_short | A structural atlas of druggable sites on Nav channels |
| title_sort | structural atlas of druggable sites on nav channels |
| topic | Nav channels structural pharmacology mode of action (MOA) analgesics anti-epilepsy drugs (AED) |
| url | https://www.tandfonline.com/doi/10.1080/19336950.2023.2287832 |
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