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

FEBS Letters

Endoh, Masao²  Takahashi, Masahiro²  Kimura, Minako²  Kondo, Kazumi¹  Ishii, Kuniaki² 

[1] Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, Japan;Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan

关键词: HERG;    Drug binding site;    Quinidine;    E-4031;    Terfenadine;   

DOI  :  10.1016/S0014-5793(01)02902-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown