› 3gnv

X-ray diffraction
2.75Å resolution

HCV NS5B polymerase in complex with 1,5 benzodiazepine inhibitor 1b

Released:
DOI: 10.2210/pdb3gnv/pdb
Model geometry
Fit model/data
PDB entry 3gnv coloured by chain, front view.
PDB entry 3gnv coloured by chain, side view.
PDB entry 3gnv coloured by chain, top view.
Source organism: Hepatitis C virus isolate HC-J4
Primary publication:
Structure-based design of a benzodiazepine scaffold yields a potent allosteric inhibitor of hepatitis C NS5B RNA polymerase.
Vandyck K, Cummings MD, Nyanguile O, Boutton CW, Vendeville S, McGowan D, Devogelaere B, Amssoms K, Last S, Rombauts K, Tahri A, Lory P, Hu L, Beauchamp DA, Simmen K, Raboisson P
J Med Chem 52 4099-102 (2009)
PMID: 19507864

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-131655 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
RNA-directed RNA polymerase Chains: A, B
Molecule details ›
Chains: A, B
Length: 581 amino acids
Theoretical weight: 64.82 KDa
Source organism: Hepatitis C virus isolate HC-J4
Expression system: Escherichia coli
UniProt:
  • Canonical: O92972 (Residues: 2420-2989; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase

Ligands and Environments

2 bound ligands:
Ligand XNZ 2 x XNZ
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P212121
Unit cell:
a: 106.291Å b: 107.965Å c: 133.799Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.177 0.174 0.234
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Privileged diazepine compounds and their emergence as bromodomain inhibitors.
Smith et al. (2014)
2 more

3 mentions without citation

1a/1b subtype profiling of nonnucleoside polymerase inhibitors of hepatitis C virus.
Nyanguile et al. (2010)
2 more