3E4C: Procaspase-1 Zymogen Domain Crystal Strucutre

One key event in inflammatory signaling is the activation of the initiator caspase, procaspase-1. Presented here is the crystal structure of the procaspase-1 zymogen without its caspase recruitment domain solved to 2.05 A. Although the isolated domain is monomeric in solution, the protein appeared dimeric in crystals. The loop arrangements in the dimer provide insight into the first autoproteolytic events that occur during activation by oligomerization. Additionally, in contrast to other caspases, we demonstrate that autoproteolysis at the second cleavage site, Asp316, is necessary for conversion to a stable dimer in solution. Critical elements of secondary structure are revealed in the crystal structure that explain why a dimeric protein is favored after proteolysis at this aspartic acid. Dimer stabilization is concurrent with a 130-fold increase in kcat, the sole contributing kinetic factor to an activated and efficient mediator of inflammation.
PDB ID: 3E4CDownload
MMDB ID: 68802
PDB Deposition Date: 2008/8/11
Updated in MMDB: 2008/12
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
Similar Structures:
Biological Unit for 3E4C: dimeric; determined by author
Molecular Components in 3E4C
Label Count Molecule
Proteins (2 molecules)
Caspase-1(Gene symbol: CASP1)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB