抗生物質 ノボビオシンは,リポポリサッカリド輸送を活性化する ATP 酵素を結合し活性化します
Janine M May1, Tristan W Owens1, Michael D Mandler1
1Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Journal of the American Chemical Society
|November 15, 2017
まとめ
抗生物質であるノボビオシンは,LPSトランスポーターATPアゼと結合することで,E. coliにおけるリポポリサッカリド (LPS) 輸送を意外に強化する. この発見は 抗生物質耐性やLPS輸送メカニズムに関する 新たな洞察をもたらします
科学分野:
- 微生物学
- 構造生物学
- 生物化学
背景:
- ノボビオシンは,グラム陽性細菌に対して有効な抗生物質ですが,外膜の透過性障壁のためにグラム陰性細菌に対して限られています.
- 抗生物質はDNAギラゼ酵素の ATPaseサブユニットを標的とする.
研究 の 目的:
- 変異したEscherichia coli菌株におけるノボビオシン耐性の増大のメカニズムを調査する.
- グラム陰性細菌におけるノボビオシンの分子標的を特定する.
主な方法:
- 浸透性のあるE. coli菌株におけるノボビオシン耐性変異体の分離と特徴づけ
- ターゲットに結合したノボビオシンの共結晶構造の決定
- 相互作用とその効果を確認するための生化学的測定と遺伝子分析.
主要な成果:
- ノボビオシン耐性を与える変異はDNAギラゼに影響を与えず,LPS輸送を誘発するATPASEを標的とした.
- ノボビオシンは,ATPaseとトランスメブランサブユニットの間のインターフェイスでLPSトランスポーターATPaseに直接結合する.
- この結合はLPSトランスポーター活性を増大させ,外膜の透過性を変化させます.
結論:
- この文脈におけるノボビオシンの主な標的は,DNAギラゼではなく,LPSトランスポーターATPaseである.
- LPSトランスポーターとの抗生物質の相互作用は,外膜の透過性を調節する.
- ノボビオシンは,LPS輸送におけるATP水解を研究するための貴重なツールとして機能する.
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