› 5twm

X-ray diffraction
1.97Å resolution

CRYSTAL STRUCTURE OF THE HEPATITIS C VIRUS GENOTYPE 2A STRAIN JFH1 L30S NS5B RNA-DEPENDENT RNA POLYMERASE IN COMPLEX WITH 5-[3-(tert-butylcarbamoyl)phenyl]-6-(ethylamino)-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide

Released:
DOI: 10.2210/pdb5twm/pdb
PDB entry 5twm coloured by chain, front view.
PDB entry 5twm coloured by chain, side view.
PDB entry 5twm coloured by chain, top view.
Source organism: Hepatitis C virus JFH-1
Primary publication:
The discovery of a pan-genotypic, primer grip inhibitor of HCV NS5B polymerase.
Eastman KJ, Parcella K, Yeung KS, Grant-Young KA, Zhu J, Wang T, Zhang Z, Yin Z, Beno BR, Sheriff S, Kish K, Tredup J, Jardel AG, Halan V, Ghosh K, Parker D, Mosure K, Fang H, Wang YK, Lemm J, Zhuo X, Hanumegowda U, Rigat K, Donoso M, Tuttle M, Zvyaga T, Haarhoff Z, Meanwell NA, Soars MG, Roberts SB, Kadow JF
Medchemcomm 8 796-806 (2017)
PMID: 30108798

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-189307 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
RNA-directed RNA polymerase Chain: A
Molecule details ›
Chain: A
Length: 574 amino acids
Theoretical weight: 63.93 KDa
Source organism: Hepatitis C virus JFH-1
Expression system: Escherichia coli
UniProt:
  • Canonical: Q99IB8 (Residues: 2443-3015; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase

Ligands and Environments

4 bound ligands:
Ligand 7NG 1 x 7NG
Ligand SO4 4 x SO4
Ligand PE5 1 x PE5
Ligand PG4 2 x PG4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2221
Unit cell:
a: 64.687Å b: 89.816Å c: 216.745Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.171 0.169 0.207
Expression system: Escherichia coli

Quick links

Citations

4 citation in other articles

Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan-genotypic HCV NS5B Polymerase Inhibitor.
Parcella et al. (2017)
3 more

2 mentions without citation

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