› 2c2o

X-ray diffraction
2.45Å resolution

Crystal structures of caspase-3 in complex with aza-peptide Michael acceptor inhibitors.

Released:
DOI: 10.2210/pdb2c2o/pdb
PDB entry 2c2o coloured by chain, front view.
PDB entry 2c2o coloured by chain, side view.
PDB entry 2c2o 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 an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position
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-154733 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Caspase-3 subunit p17 Chain: A
Molecule details ›
Chain: A
Length: 147 amino acids
Theoretical weight: 16.64 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P42574 (Residues: 29-175; Coverage: 53%)
Gene names: CASP3, CPP32
Sequence domains: Caspase domain
Structure domains: Rossmann fold
Caspase-3 subunit p12 Chain: B
Molecule details ›
Chain: B
Length: 103 amino acids
Theoretical weight: 11.98 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P42574 (Residues: 176-277; Coverage: 37%)
Gene names: CASP3, CPP32
Sequence domains: Caspase domain
Structure domains: Caspase-like
AZA-PEPTIDE INHIBITOR (5S, 8R, 11S)-14-{4-[BENZYL(METHYL) AMINO]-4-OXOBUTANOYL}-8-(2-CARBOXYETHYL)-5-(CARBOXYMETHYL)-11-(1-METHYLETHYL)-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: 789 Da
Source organism: synthetic construct
Expression system: Not provided

Ligands and Environments

No bound ligands
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ENRAF-NONIUS FR591
Spacegroup: I222
Unit cell:
a: 66.402Å b: 83.491Å c: 96.356Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.168 0.168 0.215
Expression systems:
  • Escherichia coli BL21(DE3)
  • Escherichia coli
  • Not provided

Quick links

Citations

5 review citations

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

3 mentions without citation

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