Cucurbit[8]uril Reactivation of an Inactivated Caspase-8 Mutant Reveals Differentiated Enzymatic Substrate Processing.

ABSTRACT: 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 substrat

SUBMITTER: Dang DT 

PROVIDER: S-EPMC6391946 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature