5iq6 | pdb_00005iq6

Crystal structure of Dengue virus serotype 3 RNA dependent RNA polymerase bound to HeE1-2Tyr, a new pyridobenzothizole inhibitor

spinqualitylabelsall models 5iq6, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5iq6 is a 1 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: 6CJ, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [Q6DLV0_9FLAV] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[SAAS:SAAS000336_004_099774] Publication Abstract from PubMed RNA dependent RNA polymerases (RdRp) are essential enzymes for flavivirus replication. Starting from an in silico docking analysis we identified a pyridobenzothiazole compound, HeE1-2Tyr, able to inhibit West Nile and Dengue RdRps activity in vitro, which proved effective against different flaviviruses in cell culture. Crystallographic data show that HeE1-2Tyr binds between the fingers domain and the priming loop of Dengue virus RdRp (Site 1). Conversely, enzyme kinetics, binding studies and mutational analyses suggest that, during the catalytic cycle and assembly of the RdRp-RNA complex, HeE1-2Tyr might be hosted in a distinct binding site (Site 2). RdRp mutational studies, driven by in silico docking analysis, allowed us to locate the inhibition Site 2 in the thumb domain. Taken together, our results provide innovative concepts for optimization of a new class of anti-flavivirus compounds. Targeting flavivirus RNA dependent RNA polymerase through a pyridobenzothiazole inhibitor.,Tarantino D, Cannalire R, Mastrangelo E, Croci R, Querat G, Barreca ML, Bolognesi M, Manfroni G, Cecchetti V, Milani M Antiviral Res. 2016 Sep 17;134:226-235. doi: 10.1016/j.antiviral.2016.09.007. PMID:27649989 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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