4OR4

Structure of Influenza B PB2 cap-binding domain with Q325F mutation complex with m7GDP

4OR4 の概要

• エントリーDOI: 10.2210/pdb4or4/pdb
• 関連するPDBエントリー: 4OR6 4ORO
• 分子名称: Polymerase basic protein 2, 7N-METHYL-8-HYDROGUANOSINE-5'-DIPHOSPHATE (3 entities in total)
• 機能のキーワード: cap binding, viral protein
• 由来する生物種: influenza B virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40177.81

構造登録者

Liu, Y.,Fan, J.,Zheng, X. (登録日: 2014-02-10, 公開日: 2015-02-25, 最終更新日: 2023-11-08)

主引用文献

Liu, Y.,Yang, Y.,Fan, J.,He, R.,Luo, M.,Zheng, X.
The crystal structure of the PB2 cap-binding domain of influenza B virus reveals a novel cap recognition mechanism.
J.Biol.Chem., 290:9141-9149, 2015

PubMed Abstract: The influenza RNA-dependent RNA polymerase is a core enzyme required for both transcription and replication of the virus RNA genome, making it a potential drug target for the influenza virus. To detect the feature of cap-dependent transcription of influenza B virus (FluB) polymerase, we determined the crystal structures of the wild-type FluB polymerase PB2 subunit cap-binding domain (PB2cap) with bound GDP and the mutant FluB Q325F PB2cap with bound m(7)GDP or GDP. These structures revealed that, distinct from influenza A virus (FluA) PB2cap, the guanine and ribose moieties of substrates invert in FluB PB2caps. Moreover, we characterized the substrate specificity and affinity of the PB2caps using isothermal titration calorimetry. FluB PB2cap has a weaker affinity for m(7)GDP than FluA PB2cap. Unlike FluA PB2cap that has a preference for m(7)GDP in comparison with GDP, FluB PB2cap shows an analogous affinity for both substrates. Replacement of FluB PB2 Glu(325) by Phe, the corresponding residue of FluA PB2, increased the binding affinity of FluB PB2cap for m(7)GDP to a level approximate to that of FluA PB2cap and caused a significant higher affinity to GDP. This study indicated that FluB PB2cap has a unique cap recognition mechanism compared with FluA PB2cap, providing molecular insight into inhibitor design targeting FluB PB2cap.

PubMed: 25691568
DOI: 10.1074/jbc.M115.636464

実験手法

X-RAY DIFFRACTION (2.21 Å)