› 4xbd

X-ray diffraction
1.45Å resolution

1.45A resolution structure of Norovirus 3CL protease complex with a covalently bound dipeptidyl inhibitor (1R,2S)-2-({N-[(benzyloxy)carbonyl]-3-cyclohexyl-L-alanyl}amino)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid (Orthorhombic P Form)

Released:
DOI: 10.2210/pdb4xbd/pdb
PDB entry 4xbd coloured by chain, front view.
PDB entry 4xbd coloured by chain, side view.
PDB entry 4xbd coloured by chain, top view.
Source organism: Norovirus Hu/1968/US
Primary publication:
Structure-guided design and optimization of dipeptidyl inhibitors of norovirus 3CL protease. Structure-activity relationships and biochemical, X-ray crystallographic, cell-based, and in vivo studies.
Galasiti Kankanamalage AC, Kim Y, Weerawarna PM, Uy RA, Damalanka VC, Mandadapu SR, Alliston KR, Mehzabeen N, Battaile KP, Lovell S, Chang KO, Groutas WC
J Med Chem 58 3144-55 (2015)
PMID: 25761614

Function and Biology Details

Reactions catalysed: 
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|- and the P1' position is occupied by Gly-|-
NTP + H(2)O = NDP + phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assemblies composition:
monomeric (preferred)
homo dimer
Assembly name:
PDBe Complex ID:
PDB-CPX-182856 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3C-like protease Chains: A, B
Molecule details ›
Chains: A, B
Length: 188 amino acids
Theoretical weight: 20.13 KDa
Source organism: Norovirus Hu/1968/US
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: Q83883 (Residues: 1101-1281; Coverage: 10%)
Gene name: ORF1
Structure domains: Trypsin-like serine proteases

Ligands and Environments

1 bound ligand:
Ligand M40 2 x M40
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 37.466Å b: 66.907Å c: 126.404Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.174 0.172 0.199
Expression system: Escherichia coli BL21

Quick links

Citations

10 review citations

Antiviral targets of human noroviruses.
Prasad et al. (2016)
9 more

3 mentions without citation

Structure-guided design and optimization of dipeptidyl inhibitors of norovirus 3CL protease. Structure-activity relationships and biochemical, X-ray crystallographic, cell-based, and in vivo studies.
Galasiti Kankanamalage et al. (2015)
2 more