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

doi:10.1107/S2059798316000085

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	The cap-binding site of influenza virus protein PB2 as a drug target
	Severin, Chelsea ; de Moura, Tales Rocha ; Liu, Yong ; Li, Keqin ; Zheng, Xiaofeng ; Luo, Ming
刊名	ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
	2016
关键词	antiviral inhibitor drug design broad spectrum SUBUNIT DOMAIN 1ST-IN-CLASS INHIBITOR MECHANISM REVEALS VX-787
DOI	10.1107/S2059798316000085
英文摘要	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.; Beijing Natural Science Foundation [5152012]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; SCI(E); PubMed; ARTICLE; xiaofengz@pku.edu.cn; mluo@gsu.edu; Pt 2; 245-253; 72
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/434827]
专题	生命科学学院
推荐引用方式 GB/T 7714	Severin, Chelsea,de Moura, Tales Rocha,Liu, Yong,et al. The cap-binding site of influenza virus protein PB2 as a drug target[J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY,2016.
APA	Severin, Chelsea,de Moura, Tales Rocha,Liu, Yong,Li, Keqin,Zheng, Xiaofeng,&Luo, Ming.(2016).The cap-binding site of influenza virus protein PB2 as a drug target.ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY.
MLA	Severin, Chelsea,et al."The cap-binding site of influenza virus protein PB2 as a drug target".ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2016).