4wme: Difference between revisions
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<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=4wme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wme OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wme RCSB], [http://www.ebi.ac.uk/pdbsum/4wme PDBsum]</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=4wme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wme OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wme RCSB], [http://www.ebi.ac.uk/pdbsum/4wme PDBsum]</span></td></tr> | ||
</table> | </table> | ||
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== 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> | |||
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== References == | |||
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