8be0

Early transcription elongation state of influenza B/Mem polymerase backtracked due to double incoproation of nucleotide analogue T1106 and with singly incoporated T1106 at the C +1 position

spinqualitylabelsall models 8be0, resolution 2.34Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8be0 is a 6 chain structure with sequence from Influenza B virus and Influenza B virus (B/Memphis/13/2003). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.34Å Ligands: GTA, K1F, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5V8Z9_9INFB Publication Abstract from PubMed The antiviral pseudo-base T705 and its de-fluoro analog T1106 mimic adenine or guanine and can be competitively incorporated into nascent RNA by viral RNA-dependent RNA polymerases. Although dispersed, single pseudo-base incorporation is mutagenic, consecutive incorporation causes polymerase stalling and chain termination. Using a template encoding single and then consecutive T1106 incorporation four nucleotides later, we obtained a cryogenic electron microscopy structure of stalled influenza A/H7N9 polymerase. This shows that the entire product-template duplex backtracks by 5 nt, bringing the singly incorporated T1106 to the +1 position, where it forms an unexpected T1106:U wobble base pair. Similar structures show that influenza B polymerase also backtracks after consecutive T1106 incorporation, regardless of whether prior single incorporation has occurred. These results give insight into the unusual mechanism of chain termination by pyrazinecarboxamide base analogs. Consecutive incorporation destabilizes the proximal end of the product-template duplex, promoting irreversible backtracking to a more energetically favorable overall configuration. Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106.,Kouba T, Dubankova A, Drncova P, Donati E, Vidossich P, Speranzini V, Pflug A, Huchting J, Meier C, De Vivo M, Cusack S Cell Rep. 2023 Jan 31;42(1):111901. doi: 10.1016/j.celrep.2022.111901. Epub 2023 , Jan 2. PMID:36596301 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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