Abstract

Cysteine proteases related to mammalian interleukin-1 beta converting enzyme (ICE) and to its Caenorhabditis elegans homologue, CED-3, play a critical role in the biochemical events that culminate in apoptosis. We have determined the three-dimensional structure of a complex of the human CED-3 homologue CPP32/apopain with a potent tetrapeptide-aldehyde inhibitor. The protein resembles ICE in overall structure, but its S4 subsite is strikingly different in size and chemical composition. These differences account for the variation in specificity between the ICE- and CED-3-related proteases and enable the design of specific inhibitors that can probe the physiological functions of the proteins and disease states with which they are associated.

Keywords

ProteasesTetrapeptideCaenorhabditis elegansCysteineApoptosisCell biologyMediatorEnzymeBiologyChemistryBiochemistryPeptideGene

MeSH Terms

Amino Acid SequenceApoptosisCaspase 3CaspasesCatalysisCrystallographyX-RayCysteine EndopeptidasesEnzyme PrecursorsHumansHydrogen BondingIsoenzymesModelsStructuralMolecular Sequence DataProtein ConformationProtein StructureTertiarySubstrate Specificity

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Publication Info

Year
1996
Type
article
Volume
3
Issue
7
Pages
619-625
Citations
432
Access
Closed

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Cite This

Réjean Ruel, John P. Vaillancourt, Nancy A. Thornberry et al. (1996). The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nature Structural Biology , 3 (7) , 619-625. https://doi.org/10.1038/nsb0796-619

Identifiers

DOI
10.1038/nsb0796-619
PMID
8673606

Data Quality

Data completeness: 86%