Effects of As(III) binding on α-helical structure
Effects of As(III) binding on α-helical structure
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DOI：
10.1021/ja0282644
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发表时间：
2003-03-12
影响因子：
15
通讯作者：
Schneider, JP
中科院分区：
文献类型：
--
作者：
Cline, DJ;Thorpe, C;Schneider, JP
As（III）在细胞化学中表现出广泛的作用。令人惊讶的是，砷与肽和蛋白质结合的结构后果尚不清楚。本研究利用含有两个半胱氨酸（Cys）残基在不同顺序和空间位置的模型a-螺旋肽来研究砷结合的结构效应。CD谱分析表明，对于i、i + 1、i + 2或i + 3排列，当Cys残基位于螺旋的中心或c端区域时，As（III）配位导致螺旋失稳。有趣的是，砷与i， i + 3位置的结合导致螺旋结构的消除，形成相对稳定的交替褶皱。相比之下，含有i、i + 4个Cys残基的肽具有螺旋稳定性，相应的c端和中心位置的伪成对相互作用能（DeltaG（pw）度）分别为-1.0和-0.7 kcal/mol。结合亲和和结合速率常数表明，As（III）的结合对这些中等稳定螺旋中Cys残基的位置相对不敏感。这些数据表明，As（III）结合可以是螺旋二级结构的重要调节剂。
As(III) displays a wide range of effects in cellular chemistry. Surprisingly, the structural consequences of arsenic binding to peptides and proteins are poorly understood. This study utilizes model a-helical peptides containing two cysteine (Cys) residues in various sequential arrangements and spatial locations to study the structural effects of arsenic binding. With i, and i + 1, i + 2, or i + 3 arrangements, CD spectroscopy shows that As(III) coordination causes helical destabilization when Cys residues are located at central or C-terminal regions of the helix. Interestingly, arsenic binding to i, i + 3 positions results in the elimination of helical structure and the formation of a relatively stable alternate fold. In contrast, helical stabilization is observed for peptides containing i, i + 4 Cys residues, with corresponding pseudo pairwise interaction energies (DeltaG(pw)degrees) of -1.0 and -0.7 kcal/mol for C-terminal and central placements, respectively. Binding affinities and association rate constants show that As(III) binding is comparatively insensitive to the location of the Cys residues within these moderately stable helices. These data demonstrate that As(III) binding can be a significant modulator of helical secondary structure.