PDBsum entry 4lm7

RNA binding protein

PDB id: 4lm7

Contents

Protein chain

133 a.a.

Ligands

U5P

Waters ×165

PDB id:

4lm7

Name:

RNA binding protein

Title:

Crystal structure of hcov-oc43 n-ntd complexed with ump

Structure:

Nucleoprotein. Chain: a. Fragment: unp residues 55-188. Engineered: yes

Source:

Human coronavirus. Hcov-oc43. Organism_taxid: 31631. Strain: oc43. Gene: n. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.72Å R-factor: 0.227 R-free: 0.255

Authors:

S.Y.Lin,C.L.Liu,M.H.Hou

Key ref:

S.Y.Lin et al. (2014). Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target. J Med Chem, 57, 2247-2257. PubMed id: 24564608 DOI: 10.1021/jm500089r

Date:

10-Jul-13 Release date: 28-May-14

Protein chain

P33469  (NCAP_CVHOC) -  Nucleoprotein from Human coronavirus OC43

Seq: 448 a.a.

Struc: 133 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1021/jm500089r

J Med Chem 57:2247-2257 (2014)

PubMed id: 24564608

Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target.

S.Y.Lin, C.L.Liu, Y.M.Chang, J.Zhao, S.Perlman, M.H.Hou.

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.