› 4j02

X-ray diffraction
2Å resolution

Crystal structure of hcv ns5b polymerase in complex with [(1R)-5,8-DICHLORO-1-PROPYL-1,3,4,9-TETRAHYDROPYRANO[3,4-B]INDOL-1-YL]ACETIC ACID

Released:
DOI: 10.2210/pdb4j02/pdb
PDB entry 4j02 coloured by chain, front view.
PDB entry 4j02 coloured by chain, side view.
PDB entry 4j02 coloured by chain, top view.
Source organism: Hepatitis C virus isolate HC-J4
Primary publication:
Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors.
Stammers TA, Coulombe R, Rancourt J, Thavonekham B, Fazal G, Goulet S, Jakalian A, Wernic D, Tsantrizos Y, Poupart MA, Bös M, McKercher G, Thauvette L, Kukolj G, Beaulieu PL
Bioorg Med Chem Lett 23 2585-9 (2013)
PMID: 23545108

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

3 bound ligands:
Ligand 1JE 2 x 1JE
Ligand SO4 2 x SO4
Ligand NA 2 x NA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P212121
Unit cell:
a: 105.76Å b: 108.34Å c: 133.06Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.195 0.195 0.22
Expression system: Escherichia coli

Quick links

Citations

2 review citations

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

2 mentions without citation

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