Towards a three-alpha-helix bundle protein that binds volatile general anesthetics.
Towards a three-alpha-helix bundle protein that binds volatile general anesthetics.
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寻找结合挥发性全身麻醉剂的三α螺旋束蛋白。
DOI：
10.1002/bip.20138
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Johansson,JonasS
中科院分区：
文献类型：
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作者：
Manderson,GavinA;Johansson,JonasS
全身麻醉剂氟烷和氯仿能够与合成的水溶性四α -螺旋束结合，从而模拟假定的体内受体。在这项研究中，我们研究了这些麻醉剂与合成水溶性三α螺旋束的结合。一系列变体包含多达四个X - to - Ala和多达四个X - to - Met取代；并考察了这些取代对其结构、稳定性和麻醉结合亲和力的影响。一般来说，α -螺旋的数量和三个α -螺旋束的稳定性随着X - α - Ala取代数的增加而降低。色氨酸荧光λmax同时出现红移，表明天然结构的灵活性增加。高达4个X - to - Met取代对α -螺旋的数量影响不大，但3个和4个蛋氨酸取代的变体的色氨酸λmax增加。例外是a)在三α螺旋束的一端有一簇丙氨酸和蛋氨酸残基的变体，表明这是一种可以容纳配体分子的门结构；b)具有单个Leu35Ala取代的变体，这表明在选择的位置，侧链的大小对确定麻醉剂结合亲和力很重要。©2004 Wiley期刊公司生物聚合物,2004
The general anesthetics halothane and chloroform are capable of binding to synthetic water‐soluble four‐α‐helix bundles, which model the putative in vivo receptors. In this study, we investigate the binding of these anesthetics to synthetic water‐soluble three‐α‐helix bundles. A series of variants containing up to four X‐to‐Ala and up to four X‐to‐Met substitutions was made; and the effect of these substitutions on structure, stability and anesthetic binding affinity was examined. Generally, the amount of α‐helix and the stability of the three‐α‐helix bundles decreased as the number of X‐to‐Ala substitutions increased. A concomitant red‐shift in tryptophan fluorescence λmaxwas seen, suggesting an increased flexibility of the native structure. Up to four X‐to‐Met substitutions had little effect on the amount of α‐helix, but an increase in tryptophan λmaxwas seen for the variants with three and four methionine substitutions. The exceptions were a) a variant with a clustering of alanine and methionine residues at one end of the three‐α‐helix bundle, suggesting a gate structure that can admit ligand molecules; and b) a variant with a single Leu35Ala substitution, suggesting that at select positions, the size of the side chain is important for defining anesthetic binding affinity. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004