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| | <StructureSection load='4wmf' size='340' side='right'caption='[[4wmf]], [[Resolution|resolution]] 1.97Å' scene=''> | | <StructureSection load='4wmf' size='340' side='right'caption='[[4wmf]], [[Resolution|resolution]] 1.97Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wmf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WMF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WMF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wmf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WMF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wmd|4wmd]], [[4wme|4wme]]</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=4wmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wmf OCA], [https://pdbe.org/4wmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wmf RCSB], [https://www.ebi.ac.uk/pdbsum/4wmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wmf ProSAT]</span></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=4wmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wmf OCA], [http://pdbe.org/4wmf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wmf RCSB], [http://www.ebi.ac.uk/pdbsum/4wmf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wmf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/W6A941_MERS W6A941_MERS] Catalytic subunit of viral RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate. Subsequently, the NiRAN domain transfers RNA to GDP, forming the core cap structure GpppA-RNA. The NSP14 and NSP16 methyltransferases then add methyl groups to form functional cap structures.[ARBA:ARBA00034461] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]]
| + | *[[Virus protease 3D structures|Virus protease 3D structures]] |
| - | *[[Virus protease|Virus protease]] | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mers]] | + | [[Category: Middle East respiratory syndrome-related coronavirus]] |
| - | [[Category: Lountos, G T]] | + | [[Category: Lountos GT]] |
| - | [[Category: Needle, D]] | + | [[Category: Needle D]] |
| - | [[Category: Waugh, D S]] | + | [[Category: Waugh DS]] |
| - | [[Category: 3cl protease]]
| + | |
| - | [[Category: Coronavirus]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Me]]
| + | |
| Structural highlights
Function
W6A941_MERS Catalytic subunit of viral RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9, forming a covalent RNA-protein intermediate. Subsequently, the NiRAN domain transfers RNA to GDP, forming the core cap structure GpppA-RNA. The NSP14 and NSP16 methyltransferases then add methyl groups to form functional cap structures.[ARBA:ARBA00034461]
Publication Abstract from PubMed
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus that causes severe respiratory illness accompanied by multi-organ dysfunction, resulting in a case fatality rate of approximately 40%. As found in other coronaviruses, the majority of the positive-stranded RNA MERS-CoV genome is translated into two polyproteins, one created by a ribosomal frameshift, that are cleaved at three sites by a papain-like protease and at 11 sites by a 3C-like protease (3CL(pro)). Since 3CL(pro) is essential for viral replication, it is a leading candidate for therapeutic intervention. To accelerate the development of 3CL(pro) inhibitors, three crystal structures of a catalytically inactive variant (C148A) of the MERS-CoV 3CL(pro) enzyme were determined. The aim was to co-crystallize the inactive enzyme with a peptide substrate. Fortuitously, however, in two of the structures the C-terminus of one protomer is bound in the active site of a neighboring molecule, providing a snapshot of an enzyme-product complex. In the third structure, two of the three protomers in the asymmetric unit form a homodimer similar to that of SARS-CoV 3CL(pro); however, the third protomer adopts a radically different conformation that is likely to correspond to a crystallographic monomer, indicative of substantial structural plasticity in the enzyme. The results presented here provide a foundation for the structure-based design of small-molecule inhibitors of the MERS-CoV 3CL(pro) enzyme.
Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity.,Needle D, Lountos GT, Waugh DS Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1102-11. doi:, 10.1107/S1399004715003521. Epub 2015 Apr 24. PMID:25945576[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Needle D, Lountos GT, Waugh DS. Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity. Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1102-11. doi:, 10.1107/S1399004715003521. Epub 2015 Apr 24. PMID:25945576 doi:http://dx.doi.org/10.1107/S1399004715003521
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