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| | ==Crystal structure of PLpro from Middle East Respiratory Syndrome (MERS) coronavirus== | | ==Crystal structure of PLpro from Middle East Respiratory Syndrome (MERS) coronavirus== |
| - | <StructureSection load='4rna' size='340' side='right' caption='[[4rna]], [[Resolution|resolution]] 1.79Å' scene=''> | + | <StructureSection load='4rna' size='340' side='right'caption='[[4rna]], [[Resolution|resolution]] 1.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rna]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RNA FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</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> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pt5|4pt5]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">orf1ab ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1235996 Human betacoronavirus 2c EMC/2012])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rna OCA], [http://pdbe.org/4rna PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rna RCSB], [http://www.ebi.ac.uk/pdbsum/4rna PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rna ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/K4LC41_9BETC K4LC41_9BETC]] Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity).[SAAS:SAAS014829_004_014545] Nsp9 is a ssRNA-binding protein (By similarity).[SAAS:SAAS014829_004_001449] | + | [https://www.uniprot.org/uniprot/K4LC41_MERS K4LC41_MERS] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4rna" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4rna" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human betacoronavirus 2c emc/2012]] | + | [[Category: Human betacoronavirus 2c EMC/2012]] |
| - | [[Category: Johnson, M E]] | + | [[Category: Large Structures]] |
| - | [[Category: Lee, H]] | + | [[Category: Johnson ME]] |
| - | [[Category: Lei, H]] | + | [[Category: Lee H]] |
| - | [[Category: Santarsiero, B D]] | + | [[Category: Lei H]] |
| - | [[Category: Coronavirus]] | + | [[Category: Santarsiero BD]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mer]]
| + | |
| - | [[Category: Papain-like protease]]
| + | |
| - | [[Category: Plpro]]
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| Structural highlights
Function
K4LC41_MERS
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee H, Lei H, Santarsiero BD, Gatuz JL, Cao S, Rice AJ, Patel K, Szypulinski MZ, Ojeda I, Ghosh AK, Johnson ME. Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV. ACS Chem Biol. 2015 Mar 16. PMID:25746232 doi:http://dx.doi.org/10.1021/cb500917m
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