View source for 5rej


==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with PCM-0102241==
<StructureSection load='5rej' size='340' side='right'caption='[[5rej]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REJ 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]] 1.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=T1V:1-{4-[(thiophen-2-yl)sulfonyl]piperazin-1-yl}ethan-1-one'>T1V</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=5rej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5rej OCA], [https://pdbe.org/5rej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5rej RCSB], [https://www.ebi.ac.uk/pdbsum/5rej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5rej ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments were progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease.

Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease.,Douangamath A, Fearon D, Gehrtz P, Krojer T, Lukacik P, Owen CD, Resnick E, Strain-Damerell C, Aimon A, Abranyi-Balogh P, Brandao-Neto J, Carbery A, Davison G, Dias A, Downes TD, Dunnett L, Fairhead M, Firth JD, Jones SP, Keeley A, Keseru GM, Klein HF, Martin MP, Noble MEM, O'Brien P, Powell A, Reddi RN, Skyner R, Snee M, Waring MJ, Wild C, London N, von Delft F, Walsh MA Nat Commun. 2020 Oct 7;11(1):5047. doi: 10.1038/s41467-020-18709-w. PMID:33028810<ref>PMID:33028810</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5rej" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Aimon A]]
[[Category: Brandao-Neto J]]
[[Category: Carbery A]]
[[Category: Douangamath A]]
[[Category: Dunnett L]]
[[Category: Fearon D]]
[[Category: Gehrtz P]]
[[Category: Krojer T]]
[[Category: London N]]
[[Category: Lukacik P]]
[[Category: Owen CD]]
[[Category: Powell AJ]]
[[Category: Resnick E]]
[[Category: Skyner R]]
[[Category: Snee M]]
[[Category: Strain-Damerell CM]]
[[Category: Walsh MA]]
[[Category: Wild C]]
[[Category: Von Delft F]]