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Structure-based assessment of disease- related mutations in human voltage-gated sodium channels 被引量:8
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作者 Weiyun Huang Minhao Liu +1 位作者 S. Frank Yan Nieng Yan 《Protein & Cell》 SCIE CAS CSCD 2017年第6期401-438,共38页
Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propa- gation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety ... Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propa- gation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related muta- tions have been identified in Nay channels, with Nay1.1 and Nay1.5 each harboring more than 400 mutations. Nay channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav chan- nels are required to understand their function and dis- ease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Car) channel Carl.1 provides a template for homology-based structural modeling of the evolutionarily related Nay channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Nay1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Nay channels, the analysis presented here serves as the base framework for mechanistic investi- gation of Nav channelopathies and for potential struc- ture-based drug discovery. 展开更多
关键词 Nav channels CHANNELOPATHY Navl.7 structure modeling PAIN
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