4lm7: Difference between revisions
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==Crystal structure of HCoV-OC43 N-NTD complexed with UMP== | ==Crystal structure of HCoV-OC43 N-NTD complexed with UMP== | ||
<StructureSection load='4lm7' size='340' side='right' caption='[[4lm7]], [[Resolution|resolution]] 1.72Å' scene=''> | <StructureSection load='4lm7' size='340' side='right'caption='[[4lm7]], [[Resolution|resolution]] 1.72Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4lm7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LM7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LM7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4lm7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhoc Cvhoc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LM7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LM7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lm9|4lm9]], [[4lmc|4lmc]], [[4lmt|4lmt]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lm9|4lm9]], [[4lmc|4lmc]], [[4lmt|4lmt]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">N ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31631 CVHOC])</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=4lm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lm7 OCA], [http://pdbe.org/4lm7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lm7 RCSB], [http://www.ebi.ac.uk/pdbsum/4lm7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lm7 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=4lm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lm7 OCA], [http://pdbe.org/4lm7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lm7 RCSB], [http://www.ebi.ac.uk/pdbsum/4lm7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lm7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cvhoc]] | |||
[[Category: Large Structures]] | |||
[[Category: Hou, M H]] | [[Category: Hou, M H]] | ||
[[Category: Lin, S Y]] | [[Category: Lin, S Y]] | ||
Revision as of 12:14, 3 April 2019
Crystal structure of HCoV-OC43 N-NTD complexed with UMPCrystal structure of HCoV-OC43 N-NTD complexed with UMP
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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