5cuq

Identification and characterization of novel broad spectrum inhibitors of the flavivirus methyltransferase

spinqualitylabelsall models 5cuq, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cuq is a 2 chain structure with sequence from Dengue virus 3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NSC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C0LMU0_9FLAV Publication Abstract from PubMed Flavivirus methyltransferase (MTase) is essential for viral replication. Here we report the identification of small molecules through virtual screening that putatively bind to the SAM-binding site of flavivirus MTase and inhibit its function. Six of these computationally predicted binders were identified to show significant MTase inhibition with low micromolar inhibitory activity. The most active compounds showed broad-spectrum activity against the MTase proteins of other flaviviruses. Two of these compounds also showed low cytotoxicity and high antiviral efficacy in cell-based assays. Competitive binding analyses indicated that the inhibitors performed their inhibitory function through competitive binding to the SAM cofactor binding site of the MTase. The crystal structure of the MTase-inhibitor complex further supports the mode of action and provides routes for their further optimization as flavivirus MTase inhibitors. Identification and Characterization of Novel Broad-Spectrum Inhibitors of the Flavivirus Methyltransferase.,Brecher M, Chen H, Li Z, Banavali NK, Jones SA, Zhang J, Kramer LD, Li H ACS Infect Dis. 2015;1(8):340-349. Epub 2015 Jul 27. PMID:26726314 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nonstructural protein 3D structures

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