N-ニトロゼーションメタロ酵素は,ストレプトゾトシンの薬剤分解を構成する
Tai L Ng1, Roman Rohac2, Andrew J Mitchell3
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Nature
|February 8, 2019
まとめ
科学者はSznFという 発がん剤やがん薬に含まれる N-ニトロゾ群を生成する酵素を発見しました この金属酵素は
科学分野:
- 生物化学
- 酵素学
- 有機化学
背景:
- N-ニトロゾ化合物は重要な発がん物質であり,化学療法薬である.
- N- ニトロゾ群の生物合成に責任を持つ酵素は特定されなかった.
研究 の 目的:
- N-ニトロゾ化合物の生物合成に関与する酵素を特定し,特徴づけること.
- SznFによるN-ニトロゾ群形成のメカニズムを解明する.
主な方法:
- 酵素活性の研究のための生化学的測定法
- X線結晶学を用いたSznFの構造的特徴化.
- アクティブサイト機能を調査するサイト指向型変異.
主要な成果:
- メタロ酵素であるSznFは,N-メチル-L-アルギニンからN-ニトロ尿素の生成を触媒化する.
- SznFは2つの異なる活性部位を有し,異なる鉄共因子を触媒に利用する.
- この酵素はN-N結合形成を促進し,非ヘム-鉄酵素の既知の機能を拡張する.
結論:
- SznFは,N-ニトロゾ群組成に特化した最初の特定された酵素である.
- この発見は,バクテリアのN-ニトロゾ代謝物多様性を理解するための意味を持つ新しい生物合成経路を明らかにしています.
- この研究は,N−N結合形成における金属酵素の触媒的レパートリーを拡張する.
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