› 4ih6

X-ray diffraction
2.2Å resolution

Hepatitis C Virus polymerase NS5B (BK) with fragment-based compounds

Released:
DOI: 10.2210/pdb4ih6/pdb
PDB entry 4ih6 coloured by chain, front view.
PDB entry 4ih6 coloured by chain, side view.
PDB entry 4ih6 coloured by chain, top view.
Source organism: Hepatitis C virus (isolate BK)
Primary publication:
De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.
Talamas FX, Ao-Ieong G, Brameld KA, Chin E, de Vicente J, Dunn JP, Ghate M, Giannetti AM, Harris SF, Labadie SS, Leveque V, Li J, Lui AS, McCaleb KL, Nájera I, Schoenfeld RC, Wang B, Wong A
J Med Chem 56 3115-9 (2013)
PMID: 23509929

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: 570 amino acids
Theoretical weight: 63.35 KDa
Source organism: Hepatitis C virus (isolate BK)
Expression system: Escherichia coli
UniProt:
  • Canonical: P26663 (Residues: 2421-2989; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase
Structure domains: Alpha-Beta Plaits

Ligands and Environments

1 bound ligand:
Ligand 1EP 2 x 1EP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL7-1
Spacegroup: P21
Unit cell:
a: 57.66Å b: 85.61Å c: 115.23Å
α: 90° β: 93.25° γ: 90°
R-values:
R R work R free
0.194 0.192 0.241
Expression system: Escherichia coli

Quick links

Citations

4 review citations

NMR-based approaches for the identification and optimization of inhibitors of protein-protein interactions.
Barile et al. (2014)
3 more

3 mentions without citation

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