View source for 7uue


==Structure of the SARS-CoV-2 main protease in complex with inhibitor MPI85==
<StructureSection load='7uue' size='340' side='right'caption='[[7uue]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7uue]] is a 1 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=7UUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UUE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=I65:(phenylmethyl)+~{N}-[(2~{S},3~{R})-1-[[(2~{S})-1-[2-(3-azanyl-3-oxidanylidene-propyl)-2-propanoyl-hydrazinyl]-3-cyclohexyl-1-oxidanylidene-propan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxidanylidene-butan-2-yl]carbamate'>I65</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=7uue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uue OCA], [https://pdbe.org/7uue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uue RCSB], [https://www.ebi.ac.uk/pdbsum/7uue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uue ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M(Pro)) for pathogenesis and replication. During crystallographic analyses of M(Pro) crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged post-translational cross-link that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this cross-link serves potentially as a redox switch to regulate the catalytic activity of M(Pro), a demonstrated drug target of COVID-19. The formation of this linkage leads to a much more open active site that can potentially be targeted for the development of novel SARS-CoV-2 antivirals. The structural rearrangement of M(Pro) by this cross-link indicates that small molecules that lock M(Pro) in the cross-linked form can potentially be used with other active-site-targeting molecules such as paxlovid for synergistic effects in inhibiting SARS-CoV-2 viral replication.

A Novel Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease.,Yang KS, Blankenship LR, Kuo SA, Sheng YJ, Li P, Fierke CA, Russell DH, Yan X, Xu S, Liu WR ACS Chem Biol. 2023 Mar 17;18(3):449-455. doi: 10.1021/acschembio.2c00695. Epub , 2023 Jan 11. PMID:36629751<ref>PMID:36629751</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7uue" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Liu WR]]
[[Category: Yang KS]]