バクテリアアデシンFimHを天然の多価高マノース型グリカン標的に結合させる
Maximilian M Sauer1, Roman P Jakob2, Thomas Luber3
1Institute of Molecular Biology & Biophysics , ETH Zurich , Otto-Stern-Weg 5 , CH-8093 Zurich , Switzerland.
Journal of the American Chemical Society
|December 14, 2018
まとめ
尿病原性大腸菌はFimHを使って宿主細胞と結合する. この研究は,FimHがN-グリカンとどのように相互作用するかを明らかにし,バクテリアの粘着を阻害する新しい薬の開発の洞察を提供します.
科学分野:
- 微生物学
- 構造生物学
- 生物化学
背景:
- 多価炭水化物-レクチン相互作用は宿主-病原体結合の鍵となる.
- 病原体の粘着の分子メカニズムを理解することは 抗菌薬の開発に不可欠です
研究 の 目的:
- 尿病原性エシェリキア大腸菌からのFimHと高マノースのN-グリカン間の相互作用を特徴づける.
- 開発中の抗生物質に対するFimH媒介結合の分子基礎を解明する.
主な方法:
- FimH-N-グリカン複合体の結晶構造の決定
- リガンド結合と解離の詳細な運動分析
- FimHのマルチメリゼーションと協力性の調査
主要な成果:
- FimHは,類似の親和性を有する末端α ((1-2)),α ((1-3)),およびα ((1-6) 結合マノシドを認識する.
- FimHのドメイン分離状態は,リガンド独立のドメイン関連状態よりも2000倍高い親和性を表しています.
- 一つのN-グリカンは,負の協力性を持つ最大3つのFimH分子に結合することができます.
結論:
- この研究は,尿病原性大腸菌の粘着メカニズムに関する重要な洞察を提供します.
- これらの発見は,感染と闘うのに有効なFimHアンタゴニストを設計するための堅固な基盤を提供します.
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