› 2fvc

X-ray diffraction
2Å resolution

Crystal structure of NS5B BK strain (delta 24) in complex with a 3-(1,1-Dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinone

Released:
DOI: 10.2210/pdb2fvc/pdb
PDB entry 2fvc coloured by chain, front view.
PDB entry 2fvc coloured by chain, side view.
PDB entry 2fvc coloured by chain, top view.
Source organism: Hepatitis C virus subtype 1b
Primary publication:
3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase.
Tedesco R, Shaw AN, Bambal R, Chai D, Concha NO, Darcy MG, Dhanak D, Fitch DM, Gates A, Gerhardt WG, Halegoua DL, Han C, Hofmann GA, Johnston VK, Kaura AC, Liu N, Keenan RM, Lin-Goerke J, Sarisky RT, Wiggall KJ, Zimmerman MN, Duffy KJ
J Med Chem 49 971-83 (2006)
PMID: 16451063

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:
polyprotein Chains: A, B
Molecule details ›
Chains: A, B
Length: 563 amino acids
Theoretical weight: 62.43 KDa
Source organism: Hepatitis C virus subtype 1b
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q99AU2 (Residues: 2420-2982; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase
Structure domains: Alpha-Beta Plaits

Ligands and Environments

1 bound ligand:
Ligand 888 2 x 888
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: P212121
Unit cell:
a: 85.5Å b: 105.2Å c: 126.4Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.206 0.206 0.243
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 review citations

RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.
Tian et al. (2021)
5 more

4 mentions without citation

Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors.
Kaushik-Basu et al. (2008)
3 more