› 2hai

X-ray diffraction
1.58Å resolution

Crystal structure of HCV NS5B RNA polymerase in complex with novel class of dihydropyrone-containing inhibitor.

Released:
DOI: 10.2210/pdb2hai/pdb
PDB entry 2hai coloured by chain, front view.
PDB entry 2hai coloured by chain, side view.
PDB entry 2hai coloured by chain, top view.
Source organism: Hepacivirus hominis
Primary publication:
Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.
Li H, Tatlock J, Linton A, Gonzalez J, Borchardt A, Dragovich P, Jewell T, Prins T, Zhou R, Blazel J, Parge H, Love R, Hickey M, Doan C, Shi S, Duggal R, Lewis C, Fuhrman S
Bioorg Med Chem Lett 16 4834-8 (2006)
PMID: 16824756

Function and Biology Details

Reactions catalysed: 
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-189299 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
HEPATITIS C VIRUS NS5B RNA POLYMERASE Chain: A
Molecule details ›
Chain: A
Length: 576 amino acids
Theoretical weight: 64.27 KDa
Source organism: Hepacivirus hominis
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q99AU2 (Residues: 2420-2989; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase
Structure domains: Alpha-Beta Plaits

Ligands and Environments

1 bound ligand:
Ligand PFI 1 x PFI
2 modified residues:
Ligand CSD 1 x CSD
Ligand CME 1 x CME

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL9-1
Spacegroup: P41212
Unit cell:
a: 83.255Å b: 83.255Å c: 179.83Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.215 0.215 0.236
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 review citations

Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus.
De Francesco et al. (2007)
5 more

8 mentions without citation

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