4cb7

Structure of Influenza A H5N1 PB2 cap-binding domain with bound cap analogue (compound 8e)

spinqualitylabelsall models 4cb7, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cb7 is a 2 chain structure with sequence from Influenza A virus (A/duck/Shantou/4610/2003(H5N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: 41G, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2LG68_9INFA Publication Abstract from PubMed The heterotrimeric influenza virus polymerase performs replication and transcription of viral RNA in the nucleus of infected cells. Transcription by 'cap-snatching' requires that host-cell pre-mRNAs are bound via their 5' cap to the PB2 subunit. Thus, the PB2 cap binding site is potentially a good target for new antiviral drugs that will directly inhibit viral replication. Docking studies using the structure of the PB2 cap binding domain suggested that 7-alkylguanine derivatives substituted at position N-9 and N-2 could be good candidates. Four series of 7,9-di- and 2,7,9-tri-alkyl guanine derivatives were synthesized and evaluated by an AlphaScreen assay in competition with a biotinylated cap analogue. Three synthesised compounds display potent in vitro activity with IC50 lower than 10 M. High-resolution X-ray structures of three inhibitors in complex with the H5N1 PB2 cap-binding domain confirmed the binding mode and provide detailed information for further compound optimization. New 7-methyl-guanosine derivatives targeting the influenza polymerase PB2 cap-binding domain.,Pautus S, Sehr P, Lewis J, Fortune A, Wolkerstorfer A, Szolar O, Guilligay D, Lunardi T, Decout JL, Cusack S J Med Chem. 2013 Oct 18. PMID:24134208 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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