4KQL

Hin GlmU bound to WG578

4KQL の概要

• エントリーDOI: 10.2210/pdb4kql/pdb
• 関連するPDBエントリー: 4KNR 4KNX 4KPX 4KPZ
• 分子名称: Bifunctional protein GlmU, SULFATE ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: beta helix, cell wall biosynthesis, small molecule fragment, transferase
• 由来する生物種: Haemophilus influenzae
• 細胞内の位置: Cytoplasm : P43889
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50816.94

構造登録者

Doig, P.,Kazmirski, S.L.,Boriack-Sjodin, P.A. (登録日: 2013-05-15, 公開日: 2014-10-15, 最終更新日: 2024-02-28)

主引用文献

Doig, P.,Boriack-Sjodin, P.A.,Dumas, J.,Hu, J.,Itoh, K.,Johnson, K.,Kazmirski, S.,Kinoshita, T.,Kuroda, S.,Sato, T.O.,Sugimoto, K.,Tohyama, K.,Aoi, H.,Wakamatsu, K.,Wang, H.
Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping.
Bioorg.Med.Chem., 22:6256-6269, 2014

PubMed Abstract: An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J.2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class.

PubMed: 25262942
DOI: 10.1016/j.bmc.2014.08.017

実験手法

X-RAY DIFFRACTION (2.31 Å)