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バクテリアのRNAポリメラーゼ阻害剤の新しいクラスは,核酸添加に影響を及ぼします

Irina Artsimovitch¹, Clement Chu, A Simon Lynch

¹Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA.

Science (New York, N.Y.)

|October 25, 2003

まとめ

新しい細菌のRNAポリメラーゼ (RNAP) 阻害剤は,酵素の核酸添加サイクルメカニズムを明らかにしています. これらの化合物は,RNAPの活性部位の動きに影響することによって,アロステリックで触媒を阻害します.

科学分野:

分子生物学は分子生物学である.
酵素学酵素学とは
バイオケミストリーバイオケミストリー

背景:

RNAポリメラーゼ (RNAP) は遺伝子発現に不可欠です.
RNAPの核酸添加サイクルの正確なメカニズムは,既存の構造データにもかかわらず,完全に理解されていません.

研究の目的:

細菌のRNAポリメラーゼの核酸添加サイクルメカニズムを解明する.
新型バクテリアRNAポリメラーゼ阻害剤 (CBR703シリーズ) とその作用様式を特徴づける.

主な方法:

バクテリアのRNAP阻害剤の特性 (CBR703シリーズ).
RNAPの触媒活性 (核酸添加,ピロフォスフォリシス,グレ刺激によるトランスクリプト分裂) を測定するアッセイ.
RNAPにおけるCBR703耐性突然変異の分析.

主要な成果:

CBR703化合物は,核酸添加,ピロフォスフォロリシス,およびグレ刺激によるトランスクリプト分裂を阻害する.
これらの阻害剤は,触媒から切り離された場合,RNA/DNA転位に影響を与えない.
抵抗変異は,活性部位の反対側のRNAP表面にマッピングされ,ブリッジヘリックスでリンクされます.

結論:

CBR703阻害剤は,RNAPヌクレオチド添加サイクルについての洞察を提供します.
化合物は,おそらくアロステリックに作用し,触媒作用に不可欠な活性部位の動きを阻害する.

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