5EG9

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

Summary for 5EG9

• Entry DOI: 10.2210/pdb5eg9/pdb
• Related: 5EG7 5EG8
• Descriptor: Polymerase basic protein 2 (2 entities in total)
• Functional Keywords: pb2 cap, viral protein
• Biological source: Influenza A virus
• Cellular location: Virion : Q6DNL8
• Total number of polymer chains: 2
• Total formula weight: 40995.41

Authors

Severin, C.,Rocha de Moura, T.,Liu, Y.,Li, K.,Zheng, X.,Luo, M. (deposition date: 2015-10-26, release date: 2016-02-10, Last modification date: 2023-09-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)