hERG Gating Microdomains Defined by S6 Mutagenesis and Molecular Modeling

  title={hERG Gating Microdomains Defined by S6 Mutagenesis and Molecular Modeling},
  author={Sarah L. Wynia-Smith and Anne Lynn Gillian-Daniel and Kenneth A. Satyshur and Gail A Robertson},
  journal={The Journal of General Physiology},
  pages={507 - 520}
Human ether-à-go-go-related gene (hERG) channels mediate cardiac repolarization and bind drugs that can cause acquired long QT syndrome and life-threatening arrhythmias. Drugs bind in the vestibule formed by the S6 transmembrane domain, which also contains the activation gate that traps drugs in the vestibule and contributes to their efficacy of block. Although drug-binding residues have been identified, we know little about the roles of specific S6 residues in gating. We introduced cysteine… CONTINUE READING


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