View source for 8gwe


==SARS-CoV-2 E-RTC complex with RNA-nsp9 and GMPPNP==
<StructureSection load='8gwe' size='340' side='right'caption='[[8gwe]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gwe]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GWE 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]] 2.66&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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=8gwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gwe OCA], [https://pdbe.org/8gwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gwe RCSB], [https://www.ebi.ac.uk/pdbsum/8gwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gwe ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.

A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.,Yan L, Huang Y, Ge J, Liu Z, Lu P, Huang B, Gao S, Wang J, Tan L, Ye S, Yu F, Lan W, Xu S, Zhou F, Shi L, Guddat LW, Gao Y, Rao Z, Lou Z Cell. 2022 Nov 10;185(23):4347-4360.e17. doi: 10.1016/j.cell.2022.09.037. Epub , 2022 Oct 4. PMID:36335936<ref>PMID:36335936</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8gwe" 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: Lou ZY]]
[[Category: Rao ZH]]
[[Category: Yan LM]]