› 6bqk

X-ray diffraction
1.97Å resolution

CRYSTAL STRUCTURE OF HEPATIS C VIRUS PROTEASE (NS3) COMPLEXED WITH TRIPEPTIDIC ACYL SULFONAMIDE INHIBITOR (COMPOUND 18)

Released:
DOI: 10.2210/pdb6bqk/pdb
PDB entry 6bqk coloured by chain, front view.
PDB entry 6bqk coloured by chain, side view.
PDB entry 6bqk coloured by chain, top view.
Source organism: Hepacivirus hominis
Primary publication:
Potent Inhibitors of Hepatitis C Virus NS3 Protease: Employment of a Difluoromethyl Group as a Hydrogen-Bond Donor.
Zheng B, D'Andrea SV, Sun LQ, Wang AX, Chen Y, Hrnciar P, Friborg J, Falk P, Hernandez D, Yu F, Sheaffer AK, Knipe JO, Mosure K, Rajamani R, Good AC, Kish K, Tredup J, Klei HE, Paruchuri M, Ng A, Gao Q, Rampulla RA, Mathur A, Meanwell NA, McPhee F, Scola PM
ACS Med Chem Lett 9 143-148 (2018)
PMID: 29456803

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-151107 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine protease/helicase NS3 Chains: A, B
Molecule details ›
Chains: A, B
Length: 219 amino acids
Theoretical weight: 23.26 KDa
Source organism: Hepacivirus hominis
Expression system: Escherichia coli
UniProt:
  • Canonical: P27958 (Residues: 1030-1208; Coverage: 6%)
Sequence domains: Hepatitis C virus NS3 protease
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand Z1E 2 x Z1E
Ligand ZN 2 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P21
Unit cell:
a: 48.65Å b: 68.06Å c: 61.46Å
α: 90° β: 109.58° γ: 90°
R-values:
R R work R free
0.254 0.254 0.267
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Retinoic acid receptor-related orphan receptor gamma-t (RORĪ³t) inhibitors in clinical development for the treatment of autoimmune diseases: a patent review (2016-present).
Sun et al. (2019)
2 more