› 4ju4

X-ray diffraction
2.4Å resolution

Crystal structure of hcv ns5b polymerase in complex with compound 22

Released:
DOI: 10.2210/pdb4ju4/pdb
PDB entry 4ju4 coloured by chain, front view.
PDB entry 4ju4 coloured by chain, side view.
PDB entry 4ju4 coloured by chain, top view.
Source organism: Hepatitis C virus isolate HC-J4
Primary publication:
Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay.
Stammers TA, Coulombe R, Duplessis M, Fazal G, Gagnon A, Garneau M, Goulet S, Jakalian A, LaPlante S, Rancourt J, Thavonekham B, Wernic D, Kukolj G, Beaulieu PL
Bioorg Med Chem Lett 23 6879-85 (2013)
PMID: 24176401

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-131655 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
RNA-directed RNA polymerase Chains: A, B
Molecule details ›
Chains: A, B
Length: 576 amino acids
Theoretical weight: 64.29 KDa
Source organism: Hepatitis C virus isolate HC-J4
Expression system: Escherichia coli
UniProt:
  • Canonical: O92972 (Residues: 2420-2989; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase

Ligands and Environments

2 bound ligands:
Ligand 1O3 2 x 1O3
Ligand MG 2 x MG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P212121
Unit cell:
a: 106.94Å b: 108.05Å c: 134.88Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.211 0.211 0.246
Expression system: Escherichia coli

Quick links

Citations

3 review citations

A review on HCV inhibitors: Significance of non-structural polyproteins.
Ganta et al. (2019)
2 more

1 mention without citation

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