Molecular Determinants of Voltage-dependent Human Ether-a-Go-Go Related Gene (HERG) K+ Channel Block*

@article{SnchezChapula2002MolecularDO,
  title={Molecular Determinants of Voltage-dependent Human Ether-a-Go-Go Related Gene (HERG) K+ Channel Block*},
  author={Jos{\'e} Antonio S{\'a}nchez-Chapula and Ricardo A. Navarro-Polanco and Chris Culberson and Jun Chen and Michael C Sanguinetti},
  journal={The Journal of Biological Chemistry},
  year={2002},
  volume={277},
  pages={23587 - 23595}
}
The structural determinants for the voltage-dependent block of ion channels are poorly understood. Here we investigate the voltage-dependent block of wild-type and mutant human ether-a-go-go related gene (HERG) K+ channels by the antimalarial compound chloroquine. The block of wild-type HERG channels expressed in Xenopusoocytes was enhanced as the membrane potential was progressively depolarized. The IC50 was 8.4 ± 0.9 μmwhen assessed during 4-s voltage clamp pulses to 0 mV. Chloroquine also… 

Figures from this paper

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TLDR
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The Low-Potency, Voltage-Dependent HERG Blocker Propafenone—Molecular Determinants and Drug Trapping
TLDR
Homology models of HERG based on KcsA and MthK crystal structures, representing the closed and open forms of the channel, suggest propafenone is trapped in the inner cavity and is unable to interact exclusively with Phe656 in the closed state (whereas exclusive interactions between propafanone and P he656 are found in the open-channel model).
Topological Mapping of the Asymmetric Drug Binding to the Human Ether-à-go-go-Related Gene Product (HERG) Potassium Channel by Use of Tandem Dimers
TLDR
Thermodynamic double-mutant cycle analyses revealed interactions between Tyr652 and Phe656 upon binding, and a dynamic picture of the spatial arrangements of residues that contribute to the drug-channel interaction was given.
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TLDR
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TLDR
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TLDR
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TLDR
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