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| | <StructureSection load='4lmc' size='340' side='right'caption='[[4lmc]], [[Resolution|resolution]] 1.74Å' scene=''> | | <StructureSection load='4lmc' size='340' side='right'caption='[[4lmc]], [[Resolution|resolution]] 1.74Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lmc]] 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=4LMC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LMC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lmc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_coronavirus_OC43 Human coronavirus OC43]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LMC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C5P:CYTIDINE-5-MONOPHOSPHATE'>C5P</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.742Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lm7|4lm7]], [[4lm9|4lm9]], [[4lmt|4lmt]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C5P:CYTIDINE-5-MONOPHOSPHATE'>C5P</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4lmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmc OCA], [https://pdbe.org/4lmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lmc RCSB], [https://www.ebi.ac.uk/pdbsum/4lmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lmc 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=4lmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmc OCA], [http://pdbe.org/4lmc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lmc RCSB], [http://www.ebi.ac.uk/pdbsum/4lmc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lmc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q6SA23_CVHOC Q6SA23_CVHOC]] Major structural component of virions that associates with genomic RNA to form a long, flexible, helical nucleocapsid (By similarity).[PIRNR:PIRNR003888] | + | [https://www.uniprot.org/uniprot/NCAP_CVHOC NCAP_CVHOC] Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication.[HAMAP-Rule:MF_04096] |
| | <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== |
| - | *[[Nucleoprotein|Nucleoprotein]] | + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cvhoc]] | + | [[Category: Human coronavirus OC43]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hou, M H]] | + | [[Category: Hou MH]] |
| - | [[Category: Lin, S Y]] | + | [[Category: Lin SY]] |
| - | [[Category: Liu, C L]] | + | [[Category: Liu CL]] |
| - | [[Category: Hcov-oc43]]
| + | |
| - | [[Category: N-terminal domain]]
| + | |
| - | [[Category: Nucleocapsid protein]]
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| - | [[Category: Rna binding]]
| + | |
| - | [[Category: Rna binding protein]]
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| Structural highlights
Function
NCAP_CVHOC Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication.[HAMAP-Rule:MF_04096]
Publication Abstract from PubMed
Coronaviruses (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 Also
References
- ↑ Lin SY, Liu CL, Chang YM, Zhao J, Perlman S, Hou MH. Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target. J Med Chem. 2014 Mar 27;57(6):2247-57. doi: 10.1021/jm500089r. Epub 2014 Mar 12. PMID:24564608 doi:http://dx.doi.org/10.1021/jm500089r
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