› 2c2z

X-ray diffraction
1.95Å resolution

Crystal structure of caspase-8 in complex with aza-peptide Michael acceptor inhibitor

Released:
DOI: 10.2210/pdb2c2z/pdb
PDB entry 2c2z coloured by chain, front view.
PDB entry 2c2z coloured by chain, side view.
PDB entry 2c2z coloured by chain, top view.
Source organisms:
Primary publication:
Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10.
Ekici OD, Li ZZ, Campbell AJ, James KE, Asgian JL, Mikolajczyk J, Salvesen GS, Ganesan R, Jelakovic S, Grütter MG, Powers JC
J Med Chem 49 5728-49 (2006)
PMID: 16970398

Function and Biology Details

Reaction catalysed: 
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala)
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero hexamer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-162657 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Caspase-8 subunit p18 Chain: A
Molecule details ›
Chain: A
Length: 159 amino acids
Theoretical weight: 18.03 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q14790 (Residues: 217-374; Coverage: 33%)
Gene names: CASP8, MCH5
Sequence domains: Caspase domain
Structure domains: Rossmann fold
Caspase-8 subunit p10 Chain: B
Molecule details ›
Chain: B
Length: 106 amino acids
Theoretical weight: 12.24 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q14790 (Residues: 375-479; Coverage: 22%)
Gene names: CASP8, MCH5
Sequence domains: Caspase domain
Structure domains: Caspase-like
AZA-PEPTIDE INHIBITOR (5S, 8R, 11S)-8-(2-CARBOXYETHYL) -14-[4-(3,4-DIHYDROQUINOLIN-1(2H)-YL)-4-OXOBUTANOYL] -11-[(1R)-1-HYDROXYETHYL]-5-(2-METHYLPROPYL)-3,6,9,12-TETRAOXO -1-PHENYL-2-OXA-4,7,10,13,14-PENTAAZAHEXADECAN-16-OIC ACID Chain: C
Molecule details ›
Chain: C
Length: 5 amino acids
Theoretical weight: 801 Da
Source organism: synthetic construct
Expression system: Not provided

Ligands and Environments

1 bound ligand:
Ligand DTD 1 x DTD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P3121
Unit cell:
a: 62.52Å b: 62.52Å c: 129.94Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.171 0.171 0.187
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

5 review citations

Caspase substrates and inhibitors.
Poreba et al. (2013)
4 more

5 mentions without citation

Small Molecule Active Site Directed Tools for Studying Human Caspases.
Poreba et al. (2015)
4 more