アルファヘリル構造にAs(III) の結合が及ぼす影響
Daniel J Cline1, Colin Thorpe, Joel P Schneider
1Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716-2522, USA.
Journal of the American Chemical Society
|March 6, 2003
まとめ
モデルペプチドにおけるシステイン残留物と結合する (Arsenic) は,アルファヘリル構造を不安定化し,タンパク質の折り畳みを変化させます. i,i+3のような特殊な配列はヘリを排除し,i,i+4のような配列はヘリを安定させる.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 化学生物学 化学生物学とは
背景:
- 塩素 (III) は細胞に様々な影響を及ぼしますが,タンパク質構造への影響は十分に理解されていません.
- システイン残基は,生物系におけるヒ素の重要な結合部位である.
研究 の 目的:
- アルファヘリコペプチドに結合するアルセニック (III) の構造的影響を調査する.
- システイン残留物の配置と位置が,ヒ素結合と構造変化にどのように影響するか判断する.
主な方法:
- 円形の二重化 (CD) スペクトロスコピーはペプチド二次構造の分析に使用されました.
- 異なるシステイン (Cys) 残留配列を持つモデルアルファヘリルペプチドが合成されました.
- 結合アフィニティとアソシエーションレート定数を測定した.
主要な成果:
- Cys残留物がi,i+1,i+2,またはi+3の配列で中心部またはC端末位置にあったとき,アルゼンチンの (III) 結合により不安定化されたヘリが結合した.
- i,i+3位置のCys残留にアルゼンチンを結合することで,螺旋状の構造が除去され,代替の折りたたみを形成します.
- i,i+4 Cys残基を持つペプチドの螺旋安定化が,測定された相互作用エネルギーで発生した.
- As(III) 結合親和性は,適度に安定したヘリでCysの位置にほとんど無感であった.
結論:
- (III) 結合は,アルファヘリカル二次構造を著しく調節する.
- システイン残留物の空間的配置は,ヒ素結合の構造的結果を決定する.
- これらの相互作用を理解することは,ヒ素の細胞メカニズムを理解するために不可欠です.
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