Generation of the UFM1 Toolkit for Profiling UFM1-Specific Proteases and Ligases

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2018 Sep 7

PMID 30188611

Citations 8

Authors

Katharina F Witting

Gerbrand J van der Heden van Noort

Christian Kofoed

Cami Talavera Ormeno

Dris El Atmioui

Monique P C Mulder

Huib Ovaa

Affiliations

Soon will be listed here.

Abstract

Ubiquitin-fold modifier 1 (UFM1) is a reversible post-translational modifier that is covalently attached to target proteins through an enzymatic cascade and removed by designated proteases. Abnormalities in this process, referred to as Ufmylation, have been associated with a variety of human diseases. Given this, the UFM1-specific enzymes represent potential therapeutic targets; however, understanding of their biological function has been hampered by the lack of chemical tools for activity profiling. To address this unmet need, a diversifiable platform for UFM1 activity-based probes (ABPs) utilizing a native chemical ligation (NCL) strategy was developed, enabling the generation of a variety of tools to profile both UFM1 conjugating and deconjugating enzymes. The use of the probes is demonstrated in vitro and in vivo for monitoring UFM1 enzyme reactivity, opening new research avenues.

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