4ZQQ

Apo form of influenza strain H1N1 polymerase acidic subunit N-terminal region

4ZQQ の概要

• エントリーDOI: 10.2210/pdb4zqq/pdb
• 関連するPDBエントリー: 4YYL 4ZHZ 4ZI0
• 分子名称: Polymerase acidic protein,Polymerase acidic protein, MANGANESE (II) ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22506.43

構造登録者

Fudo, S.,Yamamoto, N.,Nukaga, M.,Odagiri, T.,Tashiro, M.,Neya, S.,Hoshino, T. (登録日: 2015-05-11, 公開日: 2015-06-03, 最終更新日: 2023-11-08)

主引用文献

Fudo, S.,Yamamoto, N.,Nukaga, M.,Odagiri, T.,Tashiro, M.,Hoshino, T.
Two Distinctive Binding Modes of Endonuclease Inhibitors to the N-Terminal Region of Influenza Virus Polymerase Acidic Subunit.
Biochemistry, 55:2646-2660, 2016

PubMed Abstract: Influenza viruses are global threat to humans, and the development of new antiviral agents are still demanded to prepare for pandemics and to overcome the emerging resistance to the current drugs. Influenza polymerase acidic protein N-terminal domain (PAN) has endonuclease activity and is one of the appropriate targets for novel antiviral agents. First, we performed X-ray cocrystal analysis on the complex structures of PAN with two endonuclease inhibitors. The protein crystallization and the inhibitor soaking were done at pH 5.8. The binding modes of the two inhibitors were different from a common binding mode previously reported for the other influenza virus endonuclease inhibitors. We additionally clarified the complex structures of PAN with the same two endonuclease inhibitors at pH 7.0. In one of the crystal structures, an additional inhibitor molecule, which chelated to the two metal ions in the active site, was observed. On the basis of the crystal structures at pH 7.0, we carried out 100 ns molecular dynamics (MD) simulations for both of the complexes. The analysis of simulation results suggested that the binding mode of each inhibitor to PAN was stable in spite of the partial deviation of the simulation structure from the crystal one. Furthermore, crystal structure analysis and MD simulation were performed for PAN in complex with an inhibitor, which was already reported to have a high compound potency for comparison. The findings on the presence of multiple binding sites at around the PAN substrate-binding pocket will provide a hint for enhancing the binding affinity of inhibitors.

PubMed: 27088785
DOI: 10.1021/acs.biochem.5b01087

実験手法

X-RAY DIFFRACTION (1.8 Å)