@article{168131,
  keywords = {Animals, Humans, Mutation, Structure-Activity Relationship, Rabbits, Protein Domains, Channelopathies, NAV1.7 Voltage-Gated Sodium Channel, Calcium Channels, L-Type, NAV1.1 Voltage-Gated Sodium Channel, NAV1.5 Voltage-Gated Sodium Channel},
  author = {Weiyun Huang and Minhao Liu and Frank Yan and Nieng Yan},
  title = {Structure-based assessment of disease-related mutations in human voltage-gated sodium channels},
  abstract = {<p>Voltage-gated sodium (Na) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na channels, with Na1.1 and Na1.5 each harboring more than 400 mutations. Na channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca) channel Ca1.1 provides a template for homology-based structural modeling of the evolutionarily related Na channels. In this Resource article, we summarized all the reported disease-related mutations in human Na channels, generated a homologous model of human Na1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na channels, the analysis presented here serves as the base framework for mechanistic investigation of Na channelopathies and for potential structure-based drug discovery.</p>
},
  year = {2017},
  journal = {Protein Cell},
  volume = {8},
  pages = {401-438},
  month = {06/2017},
  issn = {1674-8018},
  doi = {10.1007/s13238-017-0372-z},
  language = {eng},
}