Inhibiting the Protein Ubiquitination Cascade by Ubiquitin-Mimicking Short Peptides

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 na...

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Bibliographic Details
Published inOrganic letters Vol. 14; no. 22; pp. 5760 - 5763
Main Authors Zhao, Bo, Choi, Chan Hee J, Bhuripanyo, Karan, Villhauer, Eric B, Zhang, Keya, Schindelin, Hermann, Yin, Jun
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 16.11.2012
Subjects
Molecular Structure
Peptides - metabolism
Ubiquitin - metabolism
Ubiquitin-Conjugating Enzymes - metabolism
Ubiquitination - drug effects
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Summary: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.
Bibliography:These authors contributed equally.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol3027736