View source for 8bf5


==Early transcription elongation state of influenza A/H7N9 polymerase stalled with incoming GTP analogue==
<StructureSection load='8bf5' size='340' side='right'caption='[[8bf5]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bf5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_B_virus Influenza B virus] 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=8BF5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BF5 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]] 2.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2P:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>G2P</scene>, <scene name='pdbligand=GTA:P1-7-METHYLGUANOSINE-P3-ADENOSINE-5,5-TRIPHOSPHATE'>GTA</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=8bf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bf5 OCA], [https://pdbe.org/8bf5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bf5 RCSB], [https://www.ebi.ac.uk/pdbsum/8bf5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bf5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5V8X3_9INFB Q5V8X3_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 8bf5" style="background-color:#fffaf0;"></div>

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