3HW4

Crystal structure of avian influenza A virus in complex with TMP

Summary for 3HW4

• Entry DOI: 10.2210/pdb3hw4/pdb
• Related: 3HW3 3HW5 3HW6
• Descriptor: Polymerase acidic protein, MAGNESIUM ION, THYMIDINE-5'-PHOSPHATE, ... (4 entities in total)
• Functional Keywords: avian influenza virus, pa_n, tmp, phosphoprotein, hydrolase
• Biological source: Influenza A virus (A/Goose/Guangdong/1/96(H5N1))
• Total number of polymer chains: 4
• Total formula weight: 122361.07

Authors

Zhao, C.,Lou, Z.,Guo, Y.,Ma, M.,Chen, Y.,Rao, Z. (deposition date: 2009-06-17, release date: 2009-11-10, Last modification date: 2023-11-01)

Primary citation

Zhao, C.,Lou, Z.,Guo, Y.,Ma, M.,Chen, Y.,Liang, S.,Zhang, L.,Chen, S.,Li, X.,Liu, Y.,Bartlam, M.,Rao, Z.
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.Virol., 83:9024-9030, 2009

PubMed Abstract: 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 Mn(2+) ion, where it mediates the interaction between bound NMPs and the N-terminal PA domain in the presence of the Mg(2+) 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.

PubMed: 19587036
DOI: 10.1128/JVI.00911-09

Experimental method

X-RAY DIFFRACTION (1.9 Å)