4K1J

Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding

4K1J の概要

• エントリーDOI: 10.2210/pdb4k1j/pdb
• 関連するPDBエントリー: 4K1H 4K1I 4K1K
• 分子名称: Neuraminidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: beta-propeller, glycoside hydrolase enzymes, hydrolase
• 由来する生物種: Influenza A virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88988.50

構造登録者

Wu, Y.,Gao, F.,Qi, J.X.,Gao, G.F. (登録日: 2013-04-05, 公開日: 2013-06-05, 最終更新日: 2020-07-29)

主引用文献

Wu, Y.,Qin, G.,Gao, F.,Liu, Y.,Vavricka, C.J.,Qi, J.,Jiang, H.,Yu, K.,Gao, G.F.
Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding
Sci Rep, 3:1551-1551, 2013

PubMed Abstract: The recently discovered 150-cavity (formed by loop residues 147-152, N2 numbering) adjacent to the enzymatic active site of group 1 influenza A neuraminidase (NA) has introduced a novel target for the design of next-generation NA inhibitors. However, only group 1 NAs, with the exception of the 2009 pandemic H1N1 NA, possess a 150-cavity, and no 150-cavity has been observed in group 2 NAs. The role of the 150-cavity played in enzymatic activity and inhibitor binding is not well understood. Here, we demonstrate for the first time that oseltamivir carboxylate can induce opening of the rigid closed N2 150-loop and provide a novel mechanism for 150-loop movement using molecular dynamics simulations. Our results provide the structural and biophysical basis of the open form of 150-loop and illustrates that the inherent flexibility and the ligand induced flexibility of the 150-loop should be taken into consideration for future drug design.

PubMed: 23531861
DOI: 10.1038/srep01551

実験手法

X-RAY DIFFRACTION (2.2 Å)