Sevoflurane-induced structural changes in a four-alpha-helix bundle protein.
Sevoflurane-induced structural changes in a four-alpha-helix bundle protein.
复制标题
七氟烷诱导四α螺旋束蛋白的结构变化。
DOI：
10.1021/bi050896q
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Johansson,JonasS
中科院分区：
文献类型：
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作者：
Pidikiti,Ravindernath;Zhang,Tao;Mallela,KrishnaMG;Shamim,Mohammad;Reddy,KondaS;Johansson,JonasS
挥发性全身麻醉剂可逆地改变中枢神经系统蛋白质功能的机制仍然不清楚。利用三种不同的光谱方法，有证据表明，现代全身麻醉剂七氟醚与模型4 -α-螺旋束蛋白的疏水核心结合导致结构变化。疏水核心中的芳香残基在麻醉剂结合后重新定向到新的环境中，蛋白质作为一个整体变得不那么动态，并表现出结构收紧。可预测的体内蛋白靶点的类似结构变化，如γ-氨基丁酸A型受体和γ-甲基-d-天冬氨酸受体，可能是这些广泛使用的临床药物的部分或全部行为效应的基础。
The mechanisms whereby volatile general anesthetics reversibly alter protein function in the central nervous system remain obscure. Using three different spectroscopic approaches, evidence is presented that binding of the modern general anesthetic sevoflurane to the hydrophobic core of a model four-α-helix bundle protein results in structural changes. Aromatic residues in the hydrophobic core reorient into new environments upon anesthetic binding, and the protein as a whole becomes less dynamic and exhibits structural tightening. Comparable structural changes in the predicted in vivo protein targets, such as the γ-aminobutyric acid type A receptor and theN-methyl-d-aspartate receptor, may underlie some, or all, of the behavioral effects of these widely used clinical agents.