Inhibiting the Protein Ubiquitination Cascade by Ubiquitin-Mimicking Short Peptides

Abstract

Short heptapeptides were identified to function as ubiquitin (UB) mimics that are activated by E1 and form thioester conjugates with E1, E2, and HECT type E3 enzymes. The activities (k(cat)/K(1/2)) of E1 with the UB-mimicking peptides are 130-1,400-fold higher than the equally long peptide with the native C-terminal sequence of UB. By forming covalent conjugates with E1, E2, and E3 enzymes, the UB-mimicking peptides can block the transfer of native UB through the cascade.