View source for 7uob


==SARS-CoV-2 replication-transcription complex bound to GTP, in a pre-catalytic state==
<StructureSection load='7uob' size='340' side='right'caption='[[7uob]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7uob]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UOB 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]] 2.68&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=L2B:3-DEOXYURIDINE-5-MONOPHOSPHATE'>L2B</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7uob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uob OCA], [https://pdbe.org/7uob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uob RCSB], [https://www.ebi.ac.uk/pdbsum/7uob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uob ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The SARS-CoV-2 RNA-dependent RNA polymerase coordinates viral RNA synthesis as part of an assembly known as the replication-transcription complex (RTC)(1). Accordingly, the RTC is a target for clinically approved antiviral nucleoside analogues, including remdesivir(2). Faithful synthesis of viral RNAs by the RTC requires recognition of the correct nucleotide triphosphate (NTP) for incorporation into the nascent RNA. To be effective inhibitors, antiviral nucleoside analogues must compete with the natural NTPs for incorporation. How the SARS-CoV-2 RTC discriminates between the natural NTPs, and how antiviral nucleoside analogues compete, has not been discerned in detail. Here, we use cryogenic-electron microscopy to visualize the RTC bound to each of the natural NTPs in states poised for incorporation. Furthermore, we investigate the RTC with the active metabolite of remdesivir, remdesivir triphosphate (RDV-TP), highlighting the structural basis for the selective incorporation of RDV-TP over its natural counterpart adenosine triphosphate(3,4). Our results explain the suite of interactions required for NTP recognition, informing the rational design of antivirals. Our analysis also yields insights into nucleotide recognition by the nsp12 NiRAN (nidovirus RdRp-associated nucleotidyltransferase), an enigmatic catalytic domain essential for viral propagation(5). The NiRAN selectively binds guanosine triphosphate, strengthening proposals for the role of this domain in the formation of the 5' RNA cap(6).

Structural basis for substrate selection by the SARS-CoV-2 replicase.,Malone BF, Perry JK, Olinares PDB, Lee HW, Chen J, Appleby TC, Feng JY, Bilello JP, Ng H, Sotiris J, Ebrahim M, Chua EYD, Mendez JH, Eng ET, Landick R, Gotte M, Chait BT, Campbell EA, Darst SA Nature. 2023 Feb;614(7949):781-787. doi: 10.1038/s41586-022-05664-3. Epub 2023 , Feb 1. PMID:36725929<ref>PMID:36725929</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7uob" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Synthetic construct]]
[[Category: Appleby TC]]
[[Category: Campbell EA]]
[[Category: Darst SA]]
[[Category: Feng JY]]
[[Category: Malone BF]]
[[Category: Perry JK]]