4lm9: Difference between revisions
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==Crystal structure of HCoV-OC43 N-NTD complexed with GMP== | ==Crystal structure of HCoV-OC43 N-NTD complexed with GMP== | ||
<StructureSection load='4lm9' size='340' side='right' caption='[[4lm9]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='4lm9' size='340' side='right' caption='[[4lm9]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lm7|4lm7]], [[4lmc|4lmc]], [[4lmt|4lmt]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lm7|4lm7]], [[4lmc|4lmc]], [[4lmt|4lmt]]</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=4lm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lm9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lm9 RCSB], [http://www.ebi.ac.uk/pdbsum/4lm9 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=4lm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lm9 OCA], [http://pdbe.org/4lm9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lm9 RCSB], [http://www.ebi.ac.uk/pdbsum/4lm9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lm9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4lm9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Nucleoprotein|Nucleoprotein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 01:19, 5 August 2016
Crystal structure of HCoV-OC43 N-NTD complexed with GMPCrystal structure of HCoV-OC43 N-NTD complexed with GMP
Structural highlights
Function[Q6SA23_CVHOC] Major structural component of virions that associates with genomic RNA to form a long, flexible, helical nucleocapsid (By similarity).[PIRNR:PIRNR003888] Publication Abstract from PubMedCoronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein's N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5'-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein's RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD-PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs. Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target.,Lin SY, Liu CL, Chang YM, Zhao J, Perlman S, Hou MH J Med Chem. 2014 Mar 27;57(6):2247-57. doi: 10.1021/jm500089r. Epub 2014 Mar 12. PMID:24564608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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