An amino acid residue whose change by mutation affects drug binding to the HERG channel

FEBS Lett. 2001 Oct 12;506(3):191-5. doi: 10.1016/s0014-5793(01)02902-7.

Abstract

We did the experiments to search for amino acids that affect quinidine binding to the HERG channel, and have identified an amino acid whose change by mutation affects the binding of various drugs. The residue is located at position 647 in the S6 and is not involved in the recently identified methanesulfonanilide binding pocket. The homology model of the HERG channel indicated that the residue faces toward the outside of the channel pore. We conclude that the residue at position 647 does not interact directly with drug molecules but plays an important role in keeping the binding site's high affinity for drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cation Transport Proteins*
  • Ether-A-Go-Go Potassium Channels
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Binding
  • Protein Conformation
  • Quinidine / metabolism*
  • Sequence Homology, Amino Acid
  • Terfenadine / metabolism*

Substances

  • Cation Transport Proteins
  • Ether-A-Go-Go Potassium Channels
  • KCNH6 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Terfenadine
  • Quinidine