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 [ | <table><tr><td colspan='2'>[[4lm7]] 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=4LM7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LM7 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72Å</td></tr> | ||
<tr><td class="sblockLbl"><b>[[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4lm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lm7 OCA], [https://pdbe.org/4lm7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lm7 RCSB], [https://www.ebi.ac.uk/pdbsum/4lm7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lm7 ProSAT]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[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 == | ||
| Line 13: | Line 16: | ||
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<ref>PMID:24564608</ref> | 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<ref>PMID:24564608</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4lm7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human coronavirus OC43]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Hou MH]] | ||
[[Category: | [[Category: Lin SY]] | ||
[[Category: | [[Category: Liu CL]] | ||
Latest revision as of 17:35, 8 November 2023
Crystal structure of HCoV-OC43 N-NTD complexed with UMPCrystal structure of HCoV-OC43 N-NTD complexed with UMP
Structural highlights
FunctionNCAP_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 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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