基板の好み 細胞壁組成の順序をスタフィロコーカス・オーレウスで確立する
Kaitlin Schaefer1,2, Tristan W Owens1, Daniel Kahne1
1Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Journal of the American Chemical Society
|February 7, 2018
まとめ
研究者は,Staphylococcus aureusの細胞壁の組み立て順序を決定しました. 壁のテイコ酸は,リガゼ結合部位におけるステリック排斥によって,合成初期にクロスリンクされたペプチドグリカンに結合する.
科学分野:
- 微生物学
- 生物化学
- 構造生物学
背景:
- グラム陽性細菌の細胞壁は 細菌の完全性にとって不可欠です
- 組み立てにはペプチドグリカンと壁のテイコ酸合成を含む複雑な生物合成経路が含まれます.
- ペプチドグリカンへの壁のテイコ酸結合の正確な順序は不明である.
研究 の 目的:
- Staphylococcus aureusの細胞壁の組み立て順序を確立するために
- 壁のテイコ酸リガゼの基質として機能するペプチドグリカン中間物質を特定する.
- これらのリガゼによる基質選択性のメカニズムを解明する.
主な方法:
- 定義されたペプチドグリカン・グリカン鎖の長さの化学合成 (クロスリンクとクロスリンク).
- ペプチドグリカン中間産物への壁のテイコ酸前駆体移転をテストする生化学的測定法
- LytR-CpsA-Psr (LCP) リガゼのX線結晶学で,壁のテイコ酸前駆体がある.
主要な成果:
- 壁のテイコ酸リガゼは,前駆物質を交結したペプチドグリカン基板に結合させることができません.
- 結晶構造は狭い結合溝を明らかにし,交結ペプチドグリカンのステリック排除を示唆する.
- キチンオリゴーマーは受容基質であり,選択性はクロスリンクされていない幹ペプチドに基づいていないことを示している.
結論:
- 壁のテイコ酸は,細胞壁合成の初期に,クロスリンクされていないペプチドグリカンと結合する.
- 交配ペプチドグリカンによるステリック阻害は,後の結合を防ぐ.
- この早期の結合は,後のペプチドグリカンクロスリンクの配置を導く可能性があります.
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