4wmd: Difference between revisions
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The | ==Crystal structure of catalytically inactive MERS-CoV 3CL protease (C148A) in spacegroup C2221== | ||
<StructureSection load='4wmd' size='340' side='right'caption='[[4wmd]], [[Resolution|resolution]] 2.58Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4wmd]] 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=4WMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WMD 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]] 2.585Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4wmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wmd OCA], [https://pdbe.org/4wmd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wmd RCSB], [https://www.ebi.ac.uk/pdbsum/4wmd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wmd ProSAT]</span></td></tr> | |||
</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;"> | |||
== 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<ref>PMID:25945576</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4wmd" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Virus protease 3D structures|Virus protease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Middle East respiratory syndrome-related coronavirus]] | |||
[[Category: Lountos GT]] | |||
[[Category: Needle D]] | |||
[[Category: Waugh DS]] | |||