› 5uj2

X-ray diffraction
2.9Å resolution

Crystal structure of HCV NS5B genotype 2A JFH-1 isolate with S15G E86Q E87Q C223H V321I mutations and Delta8 neta hairpoin loop deletion in complex with GS-639476 (diphsohate version of GS-9813), Mn2+ and symmetrical primer template 5'-AUAAAUUU

Released:
DOI: 10.2210/pdb5uj2/pdb
PDB entry 5uj2 coloured by chain, front view.
PDB entry 5uj2 coloured by chain, side view.
PDB entry 5uj2 coloured by chain, top view.
Source organisms:
Primary publication:
Discovery of a 2'-fluoro-2'-C-methyl C-nucleotide HCV polymerase inhibitor and a phosphoramidate prodrug with favorable properties.
Kirschberg TA, Metobo S, Clarke MO, Aktoudianakis V, Babusis D, Barauskas O, Birkus G, Butler T, Byun D, Chin G, Doerffler E, Edwards TE, Fenaux M, Lee R, Lew W, Mish MR, Murakami E, Park Y, Squires NH, Tirunagari N, Wang T, Whitcomb M, Xu J, Yang H, Ye H, Zhang L, Appleby TC, Feng JY, Ray AS, Cho A, Kim CU
Bioorg Med Chem Lett 27 1840-1847 (2017)
PMID: 28274633

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:
hetero trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-189320 (preferred)
Entry contents:
1 distinct polypeptide molecule
1 distinct RNA molecule
Macromolecules (2 distinct):
RNA-directed RNA polymerase Chain: A
Molecule details ›
Chain: A
Length: 572 amino acids
Theoretical weight: 63.86 KDa
Source organism: Hepacivirus hominis
Expression system: Escherichia coli
UniProt:
  • Canonical: Q99IB8 (Residues: 2443-3012; Coverage: 19%)
Sequence domains: Viral RNA dependent RNA polymerase
RNA (5'-R(*AP*UP*AP*AP*AP*UP*UP*U)-3') Chains: P, T
Molecule details ›
Chains: P, T
Length: 8 nucleotides
Theoretical weight: 2.5 KDa
Source organism: Escherichia coli
Expression system: Escherichia coli

Ligands and Environments

3 bound ligands:
Ligand MN 3 x MN
Ligand 8B4 1 x 8B4
Ligand CL 1 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-G
Spacegroup: P65
Unit cell:
a: 141.76Å b: 141.76Å c: 91.11Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.186 0.184 0.227
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Approaches to the synthesis of heterocyclic C-nucleosides.
Mukhin et al. (2023)

1 mention without citation

Structural Insights into the Binding Modes of Viral RNA-Dependent RNA Polymerases Using a Function-Site Interaction Fingerprint Method for RNA Virus Drug Discovery.
Zhao et al. (2020)