5eg9

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

spinqualitylabelsall models 5eg9, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5eg9 is a 2 chain structure with sequence from Influenza A virus (A/Ck/HK/YU22/2002(H5N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PB2_I02A6 Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Binds the cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex. In addition, participates in the inhibition of type I interferon induction through interaction with the host mitochondrial antiviral signaling protein MAVS.[UniProtKB:P03428] Publication Abstract from PubMed 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. The cap-binding site of influenza virus protein PB2 as a drug target.,Severin C, Rocha de Moura T, Liu Y, Li K, Zheng X, Luo M Acta Crystallogr D Struct Biol. 2016 Feb;72(Pt 2):245-53. doi:, 10.1107/S2059798316000085. Epub 2016 Jan 22. PMID:26894672 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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