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中子衍射揭示了金刚烷胺在甲型流感病毒M2离子通道中的阻断位点。

Neutron diffraction reveals the site of amantadine blockade in the influenza A M2 ion channel.

作者信息

Duff K C, Gilchrist P J, Saxena A M, Bradshaw J P

机构信息

Department of Biochemistry, University of Edinburgh Medical School, United Kingdom.

出版信息

Virology. 1994 Jul;202(1):287-93. doi: 10.1006/viro.1994.1345.

Abstract

The influenza A M2 protein forms proton channels which are blocked by the anti-influenza drug amantadine. Using the technique of neutron diffraction with both deuterium-labeled amantadine and influenza A M2 peptides, this study has directly located the position of interaction between the drug and the transmembrane domain of M2. Amantadine is found 0.5 nm from the center of the bilayer in an area between Val 27 and Ser 31, a location consistent with the formation of a steric block within the ion channel. Similar experiments with amantadine and an amantadine-resistant mutant peptide showed no such interaction.

摘要

甲型流感病毒M2蛋白形成质子通道,抗流感药物金刚烷胺可阻断该通道。本研究利用氘标记的金刚烷胺和甲型流感病毒M2肽进行中子衍射技术,直接确定了药物与M2跨膜结构域之间的相互作用位置。发现金刚烷胺在双层膜中心0.5纳米处,位于缬氨酸27和丝氨酸31之间的区域,该位置与离子通道内形成空间位阻一致。对金刚烷胺和金刚烷胺抗性突变肽进行的类似实验未显示出这种相互作用。

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