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Mutant HERG channel expressing cell and use thereof

机译:突变的HERG通道表达细胞及其用途

摘要

PPROBLEM TO BE SOLVED: To provide a method for three-dimensionally clarifying the interaction of a HERG channel with its inhibitor to determine the bonding position and bonding style of the inhibitor in the channel, and to provide a method for presenting the structure-modified position of the inhibitor to avoid the inhibition of the HERG channel with the inhibitor on the basis of the forecasted bonding style. PSOLUTION: A tandem dimer type protein of the -subunit of the delay rectification potassium ion channel (ISBKr/SB) of cardiac muscle cell, wherein one or both of two subunits constituting the tandem dimer are obtained by introducing a mutation to an amino acid capable of participating in the bonding of a compound inhibiting the channel, or a salt of the protein. A nucleic acid encoding the protein. An animal cell transformed with the nucleic acid. A method for forecasting the bonding style of the compound to a wild type ISBKr/SBis characterized by bringing the cell into contact with a compound inhibiting ISBKr/SBto test the inhibition of KSP+/SPchannel in the cell. PCOPYRIGHT: (C)2007,JPO&INPIT
机译:

要解决的问题:提供一种在三维上阐明HERG通道与其抑制剂的相互作用的方法,以确定该通道中抑制剂的键合位置和键合方式,并提供一种呈现结构的方法-基于预测的键合方式,改变抑制剂的位置,以避免抑制剂抑制HERG通道。

解决方案:心肌细胞延迟整流钾离子通道(I Kr )-亚基的串联二聚体型蛋白,其中获得了构成串联二聚体的两个亚基中的一个或两个通过将突变引入能够参与抑制通道的化合物或蛋白质盐结合的氨基酸上。编码蛋白质的核酸。用核酸转化的动物细胞。一种预测化合物与野生型I Kr 的键合方式的方法,其特征在于使细胞与抑制I Kr 的化合物接触以测试对K的抑制作用。单元格中的 + 通道。

版权:(C)2007,日本特许厅&INPIT

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