用截短形式的箭毒蛙毒素抑制钠离子通道功能。
Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.
作者信息
Toma Tatsuya, Logan Matthew M, Menard Frederic, Devlin A Sloan, Du Bois J
机构信息
Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
出版信息
ACS Chem Neurosci. 2016 Oct 19;7(10):1463-1468. doi: 10.1021/acschemneuro.6b00212. Epub 2016 Aug 8.
Abstract
A novel family of small molecule inhibitors of voltage-gated sodium channels (Nas) based on the structure of batrachotoxin (BTX), a well-known channel agonist, is described. Protein mutagenesis and electrophysiology experiments reveal the binding site as the inner pore region of the channel, analogous to BTX, alkaloid toxins, and local anesthetics. Homology modeling of the eukaryotic channel based on recent crystallographic analyses of bacterial Nas suggests a mechanism of action for ion conduction block.
摘要
本文描述了一类基于著名的通道激动剂——蟾毒素（BTX）结构的新型电压门控钠通道（Nas）小分子抑制剂。蛋白质诱变和电生理实验表明，其结合位点为通道的内孔区域，类似于BTX、生物碱毒素和局部麻醉剂。基于细菌Nas最近的晶体学分析对真核通道进行的同源建模揭示了离子传导阻滞的作用机制。
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本文引用的文献
1
Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications.
J Med Chem. 2015 Sep 24;58(18):7093-118. doi: 10.1021/jm501981g. Epub 2015 May 14.
2
Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart.
J Mol Biol. 2015 Jan 16;427(1):3-30. doi: 10.1016/j.jmb.2014.08.010. Epub 2014 Aug 23.
3
Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels.
Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):E2724-32. doi: 10.1073/pnas.1220844110. Epub 2013 Jul 1.
4
Modular Synthesis of the Pentacyclic Core of Batrachotoxin and Select Batrachotoxin Analogue Designs.
Chem Sci. 2013 Mar 1;4(3):1059-1063. doi: 10.1039/C2SC21723F.
5
Conformer generation with OMEGA: learning from the data set and the analysis of failures.
J Chem Inf Model. 2012 Nov 26;52(11):2919-36. doi: 10.1021/ci300314k. Epub 2012 Nov 12.
6
Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing.
Nat Commun. 2012;3:1102. doi: 10.1038/ncomms2077.
7
Advances in targeting voltage-gated sodium channels with small molecules.
ChemMedChem. 2012 Oct;7(10):1712-40. doi: 10.1002/cmdc.201200298. Epub 2012 Sep 4.
8
Crystal structure of a voltage-gated sodium channel in two potentially inactivated states.
Nature. 2012 May 20;486(7401):135-9. doi: 10.1038/nature11077.
9
Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel.
Nature. 2012 May 20;486(7401):130-4. doi: 10.1038/nature11054.
10
Neurotoxins and their binding areas on voltage-gated sodium channels.
Front Pharmacol. 2011 Nov 9;2:71. doi: 10.3389/fphar.2011.00071. eCollection 2011.
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