5y3e: Difference between revisions

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-'''Unreleased structure'''
-The entry 5y3e is ON HOLD  until Paper Publication
+==Crystal structure of SARS coronavirus papain-like protease in complex with glycerol==
+<StructureSection load='5y3e' size='340' side='right'caption='[[5y3e]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5y3e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y3E 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]] 1.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5y3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y3e OCA], [https://pdbe.org/5y3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y3e RCSB], [https://www.ebi.ac.uk/pdbsum/5y3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y3e ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/R1A_SARS R1A_SARS] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.  Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371).<ref>PMID:23035226</ref> <ref>PMID:30943371</ref>   May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.<ref>PMID:19640993</ref>   Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling.<ref>PMID:16271890</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> <ref>PMID:24622840</ref> <ref>PMID:24410069</ref>   Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.<ref>PMID:23943763</ref> <ref>PMID:24410069</ref>   Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH.[PROSITE-ProRule:PRU00772]<ref>PMID:16226257</ref>   Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833).<ref>PMID:24991833</ref> <ref>PMID:24410069</ref>   Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.<ref>PMID:22039154</ref>   Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.<ref>PMID:22039154</ref>   May participate in viral replication by acting as a ssRNA-binding protein.<ref>PMID:19153232</ref>   Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.<ref>PMID:22635272</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in southern China in late 2002 and caused a global outbreak with a fatality rate around 10% in 2003. Ten years later, a second highly pathogenic human CoV, MERS-CoV, emerged in the Middle East and has spread to other countries in Europe, North Africa, North America and Asia. As of November 2017, MERS-CoV had infected at least 2102 people with a fatality rate of about 35% globally, and hence there is an urgent need to identify antiviral drugs that are active against MERS-CoV. Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PL(pro)s) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PL(pro) but as a competitive (or mixed) inhibitor of SARS-CoV PL(pro). The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PL(pro) by disulfiram, while synergistic inhibition of MERS-CoV PL(pro) by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs.
-Authors: Lin, M.H., Chou, C.Y.
+Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes.,Lin MH, Moses DC, Hsieh CH, Cheng SC, Chen YH, Sun CY, Chou CY Antiviral Res. 2017 Dec 28;150:155-163. doi: 10.1016/j.antiviral.2017.12.015. PMID:29289665<ref>PMID:29289665</ref>
-Description: Crystal structure of SARS coronavirus papain-like protease in complex with glycerol
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chou, C.Y]]
+<div class="pdbe-citations 5y3e" style="background-color:#fffaf0;"></div>
-[[Category: Lin, M.H]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Severe acute respiratory syndrome-related coronavirus]]
+[[Category: Chou CY]]
+[[Category: Lin MH]]