› 4obc

X-ray diffraction
2.5Å resolution

Crystal structure of HCV polymerase NS5b genotype 2a JFH-1 isolate with the S15G, C223H, V321I resistance mutations against the guanosine analog GS-0938 (PSI-3529238)

Released:
DOI: 10.2210/pdb4obc/pdb
PDB entry 4obc coloured by chain, front view.
PDB entry 4obc coloured by chain, side view.
PDB entry 4obc coloured by chain, top view.
Source organism: Hepatitis C virus JFH-1
Primary publication:
Molecular and structural basis for the roles of hepatitis C virus polymerase NS5B amino acids 15, 223, and 321 in viral replication and drug resistance.
Lam AM, Edwards TE, Mosley RT, Murakami E, Bansal S, Lugo C, Bao H, Otto MJ, Sofia MJ, Furman PA
Antimicrob Agents Chemother 58 6861-9 (2014)
PMID: 25182647

Function and Biology Details

Reactions catalysed: 
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
NTP + H(2)O = NDP + phosphate
ATP + H(2)O = ADP + phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-189307 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
RNA-directed RNA polymerase Chain: A
Molecule details ›
Chain: A
Length: 580 amino acids
Theoretical weight: 64.82 KDa
Source organism: Hepatitis C virus JFH-1
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q99IB8 (Residues: 2443-3012; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase

Ligands and Environments

4 bound ligands:
Ligand MES 1 x MES
Ligand GOL 2 x GOL
Ligand PG6 1 x PG6
Ligand CL 1 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL9-2
Spacegroup: P65
Unit cell:
a: 140.208Å b: 140.208Å c: 92.567Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.19 0.188 0.223
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Structure and function of Zika virus NS5 protein: perspectives for drug design.
Wang et al. (2018)
5 other articles

3 mentions without citation

RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution.
Venkataraman et al. (2018)
2 more