マルチドラッグトランスポーターのトランスクリプションアクティベーターであるBmrRによるマルチドラッグ認識の構造的基礎
E E Zheleznova1, P N Markham, A A Neyfakh
1Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Cell
|February 20, 1999
まとめ
バシルス・サブティリスのBmrRタンパク質は,アルファヘリクスを展開してポケットを露出させることで,さまざまな薬を結合します. この結合メカニズムは,水性および静電相互作用を伴うもので,多剤耐性の鍵です.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
背景:
- マルチドラッグ・エフフリュース・トランスポーターは,様々な毒素を認識します.
- バシルス・サブティリスの転写レギュレータBmrRは,水害性カチオン性薬剤に結合する.
- BmrRは,薬物結合時にマルチドラッグトランスポーターBmrの発現を活性化する.
研究 の 目的:
- BmrRによる薬物結合の構造的基礎を解明する.
- BmrRにおける薬物認識と選択性のメカニズムを理解する.
主な方法:
- BmrRの多剤結合ドメインのX線結晶学.
- BmrR-テトラフェニルフォスフォニウム複合体の結晶構造の決定,分別2.7Aと2.8Aの解像度.
主要な成果:
- 薬物結合は,BmrRのアルファヘリクスの展開と移転を誘導する.
- 内部の薬物結合ポケットは,ヘリックス運動時に露出します.
- テトラフェニルフォスフォニウム結合は,カチオン選択性のために埋もれたグルタミン酸残留物との重要な相互作用を含む,水性および静電的相互作用を含む.
結論:
- BmrRは,結合のために,薬物によって引き起こされたユニークな形状の変化を採用しています.
- 埋められたグルタミン酸残留は,BmrRのカチオン選択性にとって重要である.
- 同様の結合原理は,他の多剤結合タンパク質にも適用できる.
関連する概念動画
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