View source for 8bdr


==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 U +1 position==
<StructureSection load='8bdr' size='340' side='right'caption='[[8bdr]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bdr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Acre/117700/2012) Influenza B virus (B/Acre/117700/2012)], [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Acre/117701/2012) Influenza B virus (B/Acre/117701/2012)], [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Kaliningrad/RII06/2012) Influenza B virus (B/Kaliningrad/RII06/2012)] and [https://en.wikipedia.org/wiki/Influenza_B_virus_(B/Memphis/13/2003) Influenza B virus (B/Memphis/13/2003)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BDR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTA:P1-7-METHYLGUANOSINE-P3-ADENOSINE-5,5-TRIPHOSPHATE'>GTA</scene>, <scene name='pdbligand=K1F:[(2R,3S,4R,5R)-5-(3-aminocarbonyl-2-oxidanylidene-pyrazin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>K1F</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8bdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdr OCA], [https://pdbe.org/8bdr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdr RCSB], [https://www.ebi.ac.uk/pdbsum/8bdr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5V8Z9_9INFB Q5V8Z9_9INFB] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:36596301</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bdr" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Cusack S]]
[[Category: Kouba T]]