View source for 9bf8


==SARS-CoV-2 Papain-like Protease (PLpro) Untagged Crystal Structure==
<StructureSection load='9bf8' size='340' side='right'caption='[[9bf8]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bf8]] 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=9BF8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BF8 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=9bf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bf8 OCA], [https://pdbe.org/9bf8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bf8 RCSB], [https://www.ebi.ac.uk/pdbsum/9bf8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bf8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A859GWA9_SARS2 A0A859GWA9_SARS2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
COVID-19 is caused by SARS-CoV-2, a highly transmissible and pathogenic RNA betacoronavirus. Developing small-molecule antiviral inhibitors of the SARS-CoV-2 papain-like protease (PL (pro) ) is advantageous due to the enzyme's role in processing viral polyproteins and disrupting host immune sensing. Given the structural and functional similarities between PL (pro) and human deubiquitinases (DUBs), small-molecule inhibitors are frequently counter-screened for off-target activity using a panel of human DUBs. Through X-ray crystallography, DALI structural comparisons, and in silico analysis, a high-quality crystal structure of SARS-CoV-2 PL (pro) enabled the identification of the closest structural human homologues of PL (pro) . Among the 27 human DUBs identified, USP46 and USP12 displayed the greatest structural similarity to PL (pro) , with alignment scores below 0.45 and RMSD values of 3.0 A or less. Additionally, binding sites on ubiquitin-specific protease (USP46) and USP12, ancillary to the active site residues, share high sequence identity to the PL (pro) substrate binding sites that are often engaged by the most potent PL (pro) inhibitors. These findings offer a strong basis for choosing anti-targets and serve as a foundation for designing selective small-molecule PL (pro) inhibitors.

Human Structural Homologues of SARS-CoV-2 PL (pro) as Anti-Targets: A Strategic Panel Analysis.,Al-Homoudi AI, Engel J, Muczynski MD, Brunzelle JS, Gavande NS, Kovari LC MicroPubl Biol. 2025 Apr 14;2025:10.17912/micropub.biology.001418. doi: , 10.17912/micropub.biology.001418. eCollection 2025. PMID:40297819<ref>PMID:40297819</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bf8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Al-Homoudi AI]]
[[Category: Brunzelle JS]]
[[Category: Engel J]]
[[Category: Gavande N]]
[[Category: Kovari LC]]