5EG7

The cap binding site of influenza virus protein PB2 as a drug target

5EG7 の概要

• エントリーDOI: 10.2210/pdb5eg7/pdb
• 関連するPDBエントリー: 5EG8 5EG9
• 分子名称: Polymerase basic protein 2, 7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pb2 cap, viral protein
• 由来する生物種: Influenza A virus
• 細胞内の位置: Host nucleus : G3LZH2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18669.26

構造登録者

Severin, C.,Rocha de Moura, T.,Liu, Y.,Li, K.,Zheng, X.,Luo, M. (登録日: 2015-10-26, 公開日: 2016-02-10, 最終更新日: 2023-09-27)

主引用文献

Severin, C.,Rocha de Moura, T.,Liu, Y.,Li, K.,Zheng, X.,Luo, M.
The cap-binding site of influenza virus protein PB2 as a drug target.
Acta Crystallogr D Struct Biol, 72:245-253, 2016

PubMed Abstract: The RNA polymerase of influenza virus consists of three subunits: PA, PB1 and PB2. It uses a unique `cap-snatching' mechanism for the transcription of viral mRNAs. The cap-binding domain of the PB2 subunit (PB2cap) in the viral polymerase binds the cap of a host pre-mRNA molecule, while the endonuclease of the PA subunit cleaves the RNA 10-13 nucleotides downstream from the cap. The capped RNA fragment is then used as the primer for viral mRNA transcription. The structure of PB2cap from influenza virus H1N1 A/California/07/2009 and of its complex with the cap analog m(7)GTP were solved at high resolution. Structural changes are observed in the cap-binding site of this new pandemic influenza virus strain, especially the hydrophobic interactions between the ligand and the target protein. m(7)GTP binds deeper in the pocket than some other virus strains, much deeper than the host cap-binding proteins. Analysis of the new H1N1 structures and comparisons with other structures provide new insights into the design of small-molecule inhibitors that will be effective against multiple strains of both type A and type B influenza viruses.

PubMed: 26894672
DOI: 10.1107/S2059798316000085

実験手法

X-RAY DIFFRACTION (1.4 Å)