› 4eo8

X-ray diffraction
1.8Å resolution

HCV NS5B polymerase inhibitors: Tri-substituted acylhydrazines as tertiary amide bioisosteres

Released:
DOI: 10.2210/pdb4eo8/pdb
PDB entry 4eo8 coloured by chain, front view.
PDB entry 4eo8 coloured by chain, side view.
PDB entry 4eo8 coloured by chain, top view.
Source organism: Hepatitis C virus (isolate BK)
Primary publication:
Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors.
Canales E, Carlson JS, Appleby T, Fenaux M, Lee J, Tian Y, Tirunagari N, Wong M, Watkins WJ
Bioorg Med Chem Lett 22 4288-92 (2012)
PMID: 22664130

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-150808 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
RNA-directed RNA polymerase Chains: A, B
Molecule details ›
Chains: A, B
Length: 577 amino acids
Theoretical weight: 64.14 KDa
Source organism: Hepatitis C virus (isolate BK)
Expression system: Escherichia coli
UniProt:
  • Canonical: P26663 (Residues: 2422-2989; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase
Structure domains: Alpha-Beta Plaits

Ligands and Environments

1 bound ligand:
Ligand 0S3 2 x 0S3
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P212121
Unit cell:
a: 85.59Å b: 105.93Å c: 126.72Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.18 0.179 0.22
Expression system: Escherichia coli

Quick links

Citations

4 review citations

Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.
Ruiz-Castillo et al. (2016)
3 more

4 mentions without citation

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