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	Nucleoside Monophosphate Complex Structures of the Endonuclease Domain from the Influenza Virus Polymerase PA Subunit Reveal the Substrate Binding Site inside the Catalytic Center
	Zhao, Cong ; Lou, Zhiyong ; Guo, Yu ; Ma, Ming ; Chen, Yutao ; Liang, Shuaiyi ; Zhang, Liang ; Chen, Shoudeng ; Li, Xuemei ; Liu, Yingfang ; Bartlam, Mark ; Rao, Zihe
	2010-10-12 ; 2010-10-12
关键词	RNA-POLYMERASE CAP-BINDING CRYSTAL-STRUCTURE INHIBITORS SOFTWARE RESIDUES MOTIFS PB2 Virology
中文摘要	Highly pathogenic influenza virus strains currently in circulation pose a significant risk of a global pandemic. Following the reported crystal structure of the endonuclease domain from the avian influenza virus polymerase PA subunit, here we report the results of a systematic X-ray crystallographic analysis of its complex with adenosine, uridine, and thymidine nucleoside monophosphates (NMPs). Electron density corresponding to the monophosphate moiety of each nucleotide was apparent in each NMP complex and bound to the catalytic metal. A hydrophobic site was found to contribute to nucleoside binding. The NMP complex structures should represent the conformation of the bound product after nuclease cleavage. Moreover, one solvent molecule was found to occupy an equivalent position to the second reported Mn2+ ion, where it mediates the interaction between bound NMPs and the N-terminal PA domain in the presence of the Mg2+ ion. The results presented here indicate a possible cleavage mechanism and identify a distinct nucleotide binding pocket. The identification of this binding pocket opens a new avenue for anti-influenza drug discovery, targeting the cap-dependent endonuclease, in response to the worldwide threat of influenza.
语种	英语 ; 英语
出版者	AMER SOC MICROBIOLOGY ; WASHINGTON ; 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/78714]
专题	清华大学
推荐引用方式 GB/T 7714	Zhao, Cong,Lou, Zhiyong,Guo, Yu,et al. Nucleoside Monophosphate Complex Structures of the Endonuclease Domain from the Influenza Virus Polymerase PA Subunit Reveal the Substrate Binding Site inside the Catalytic Center[J],2010, 2010.
APA	Zhao, Cong.,Lou, Zhiyong.,Guo, Yu.,Ma, Ming.,Chen, Yutao.,...&Rao, Zihe.(2010).Nucleoside Monophosphate Complex Structures of the Endonuclease Domain from the Influenza Virus Polymerase PA Subunit Reveal the Substrate Binding Site inside the Catalytic Center..
MLA	Zhao, Cong,et al."Nucleoside Monophosphate Complex Structures of the Endonuclease Domain from the Influenza Virus Polymerase PA Subunit Reveal the Substrate Binding Site inside the Catalytic Center".(2010).

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