View source for 4rna


==Crystal structure of PLpro from Middle East Respiratory Syndrome (MERS) coronavirus==
<StructureSection load='4rna' size='340' side='right'caption='[[4rna]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rna]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_betacoronavirus_2c_EMC/2012 Human betacoronavirus 2c EMC/2012]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RNA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RNA 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]] 1.794&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</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=4rna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rna OCA], [https://pdbe.org/4rna PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rna RCSB], [https://www.ebi.ac.uk/pdbsum/4rna PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rna ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/K4LC41_MERS K4LC41_MERS] 
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== Publication Abstract from PubMed ==
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC50 of 6 muM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC50 of 11 muM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3).

Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV.,Lee H, Lei H, Santarsiero BD, Gatuz JL, Cao S, Rice AJ, Patel K, Szypulinski MZ, Ojeda I, Ghosh AK, Johnson ME ACS Chem Biol. 2015 Mar 16. PMID:25746232<ref>PMID:25746232</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4rna" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Human betacoronavirus 2c EMC/2012]]
[[Category: Large Structures]]
[[Category: Johnson ME]]
[[Category: Lee H]]
[[Category: Lei H]]
[[Category: Santarsiero BD]]