› 3m5m

X-ray diffraction
1.7Å resolution

Avoiding drug resistance against HCV NS3/4A protease inhibitors

Released:
DOI: 10.2210/pdb3m5m/pdb
PDB entry 3m5m coloured by chain, front view.
PDB entry 3m5m coloured by chain, side view.
PDB entry 3m5m coloured by chain, top view.
Source organism: hepatitis C virus genotype 1a
Primary publication:
Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding.
Romano KP, Ali A, Royer WE, Schiffer CA
Proc Natl Acad Sci U S A 107 20986-91 (2010)
PMID: 21084633

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

Assemblies composition:
monomeric (preferred)
hetero dimer
Assembly name:
PDBe Complex ID:
PDB-CPX-108606 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
NS3/4A Chains: A, B
Molecule details ›
Chains: A, B
Length: 203 amino acids
Theoretical weight: 21.49 KDa
Source organism: hepatitis C virus genotype 1a
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: A8DG50 (Residues: 1013-1017, 1018-1208; Coverage: 7%)
Sequence domains: Hepatitis C virus NS3 protease
Structure domains:
FDEMEEC Peptide Chain: C
Molecule details ›
Chain: C
Length: 8 amino acids
Theoretical weight: 928 Da
Source organism: hepatitis C virus genotype 1a
Expression system: Not provided
UniProt:
  • Canonical: Q9WPH5 (Residues: 1706-1712; Coverage: 0%)

Ligands and Environments

3 bound ligands:
Ligand MES 1 x MES
Ligand SO4 3 x SO4
Ligand ZN 2 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 14-BM-C
Spacegroup: P212121
Unit cell:
a: 58.218Å b: 60.093Å c: 95.67Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.178 0.177 0.206
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

25 review citations

Rational approaches to improving selectivity in drug design.
Huggins et al. (2012)
24 more

9 mentions without citation

Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors.
Özen et al. (2019)
8 more