4LMC

Crystal structure of HCoV-OC43 N-NTD complexed with CMP

4LMC の概要

• エントリーDOI: 10.2210/pdb4lmc/pdb
• 関連するPDBエントリー: 4LM7 4LM9 4LMT
• 分子名称: Nucleoprotein, CYTIDINE-5'-MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: hcov-oc43, nucleocapsid protein, n-terminal domain, rna binding, rna binding protein
• 由来する生物種: Human coronavirus (HCoV-OC43)
• 細胞内の位置: Virion: Q6SA23
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15674.02

構造登録者

Lin, S.Y.,Liu, C.L.,Hou, M.H. (登録日: 2013-07-10, 公開日: 2014-05-28, 最終更新日: 2023-11-08)

主引用文献

Lin, S.Y.,Liu, C.L.,Chang, Y.M.,Zhao, J.,Perlman, S.,Hou, M.H.
Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target
J.Med.Chem., 57:2247-2257, 2014

PubMed Abstract: 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.

PubMed: 24564608
DOI: 10.1021/jm500089r

実験手法

X-RAY DIFFRACTION (1.742 Å)