Cucurbit[8]uril reactivation of an inactivated caspase-8 mutant reveals differentiated enzymatic substrate processing

Dung T. Dang, Arthur H.A.M. van Onzen, Yvonne L. Dorland, Luc Brunsveld

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
73 Downloads (Pure)


Caspase-8 constructs featuring an N-terminal FGG sequence allow for selective twofold recognition by cucurbit[8]uril, which leads to an increase of the enzymatic activity in a cucurbit[8]uril dose-dependent manner. This supramolecular switching has enabled for the first time the study of the same caspase-8 in its two extreme states; as full monomer and as cucurbit[8]uril induced dimer. A mutated, fully monomeric caspase-8 (D384A), which is enzymatically inactive towards its natural substrate caspase-3, could be fully reactivated upon addition of cucurbit[8]uril. In its monomeric state caspase-8 (D384A) still processes a small synthetic substrate, but not the natural caspase-3 substrate, highlighting the close interplay between protein dimerization and active site rearrangement for substrate selectivity. The ability to switch the caspase-8 activity by a supramolecular system thus provides a flexible approach to studying the activity of a protein at different oligomerization states.

Original languageEnglish
Pages (from-to)2490-2494
Number of pages5
Issue number23
Publication statusPublished - 4 Dec 2018


  • caspases
  • cucurbit[8]uril
  • protein assembly
  • protein engineering
  • supramolecular chemistry
  • Enzyme Reactivators/chemistry
  • Catalysis/drug effects
  • Imidazoles/chemistry
  • Protein Multimerization/drug effects
  • Humans
  • Bridged-Ring Compounds/chemistry
  • Point Mutation
  • Caspase 8/genetics


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