4kxj

<StructureSection load='4kxj' size='340' side='right' caption='[[4kxj]], [[Resolution|resolution]] 2.65&Aring;' scene=''>

<table><tr><td colspan='2'>[[4kxj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KXJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KXJ FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P34:N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE'>P34</scene></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=4kxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kxj OCA], [http://pdbe.org/4kxj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kxj RCSB], [http://www.ebi.ac.uk/pdbsum/4kxj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kxj ProSAT]</span></td></tr>

[[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]

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<ref>PMID:24564608</ref>

 

*[[Nucleoprotein|Nucleoprotein]]

[[Category: Hou, M H]]

[[Category: Lin, S Y]]

[[Category: Hcov-oc43 n-ntd]]

[[Category: N-protein ligand]]

[[Category: Rna binding protein]]