4o4r

Murine Norovirus RdRp in complex with PPNDS

spinqualitylabelsall models 4o4r, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4o4r is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 20V, SO4 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Norovirus (NV) is a major cause of gastroenteritis worldwide. Antivirals against such important pathogens are on demand. Among the viral proteins that orchestrate viral replication, RNA-dependent-RNA-polymerase (RdRp) is a promising drug development target. From an in silico-docking search focused on the RdRp active site, we selected the compound PPNDS, which showed low micromolar IC50vs. murine NV-RdRp in vitro. We report the crystal structure of the murine NV-RdRp/PPNDS complex showing that two molecules of the inhibitor bind in antiparallel stacking interaction, properly oriented to block exit of the newly synthesized RNA. Such inhibitor-binding mode mimics two stacked nucleotide-bases of the RdRp/ssRNA complex. PPNDS inhibits murine Norovirus RNA-dependent RNA-polymerase mimicking two RNA stacking bases.,Croci R, Tarantino D, Milani M, Pezzullo M, Rohayem J, Bolognesi M, Mastrangelo E FEBS Lett. 2014 May 2;588(9):1720-5. doi: 10.1016/j.febslet.2014.03.021. Epub, 2014 Mar 18. PMID:24657439 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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