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New page: ==PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with PCM-0102201== <StructureSection load='5rep' size='340' side='right'caption='5rep, [... |
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<StructureSection load='5rep' size='340' side='right'caption='[[5rep]], [[Resolution|resolution]] 1.81Å' scene=''> | <StructureSection load='5rep' size='340' side='right'caption='[[5rep]], [[Resolution|resolution]] 1.81Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5REP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5REP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=T3G:1-{4-[(2,6-difluorophenyl)sulfonyl]piperazin-1-yl}ethan-1-one'>T3G</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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=T3G:1-{4-[(2,6-difluorophenyl)sulfonyl]piperazin-1-yl}ethan-1-one'>T3G</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=5rep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5rep OCA], [https://pdbe.org/5rep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5rep RCSB], [https://www.ebi.ac.uk/pdbsum/5rep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5rep ProSAT]</span></td></tr> | |||
</table> | </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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5rep" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Virus protease 3D structures|Virus protease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Aimon | [[Category: Aimon A]] | ||
[[Category: Brandao-Neto | [[Category: Brandao-Neto J]] | ||
[[Category: Carbery | [[Category: Carbery A]] | ||
[[Category: Douangamath A]] | |||
[[Category: Douangamath | [[Category: Dunnett L]] | ||
[[Category: Dunnett | [[Category: Fearon D]] | ||
[[Category: Fearon | [[Category: Gehrtz P]] | ||
[[Category: Gehrtz | [[Category: Krojer T]] | ||
[[Category: Krojer | [[Category: London N]] | ||
[[Category: London | [[Category: Lukacik P]] | ||
[[Category: Lukacik | [[Category: Owen CD]] | ||
[[Category: Owen | [[Category: Powell AJ]] | ||
[[Category: Powell | [[Category: Resnick E]] | ||
[[Category: Resnick | [[Category: Skyner R]] | ||
[[Category: Skyner | [[Category: Snee M]] | ||
[[Category: Snee | [[Category: Strain-Damerell CM]] | ||
[[Category: Strain-Damerell | [[Category: Walsh MA]] | ||
[[Category: Walsh | [[Category: Wild C]] | ||
[[Category: Wild | [[Category: Von Delft F]] | ||
[[Category: | |||
Latest revision as of 12:22, 23 October 2024
PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with PCM-0102201PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with PCM-0102201
Structural highlights
Publication Abstract from PubMedCOVID-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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