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Generation of the UFM1 Toolkit for Profiling UFM1‐Specific Proteases and Ligases
Author(s) -
Witting Katharina F.,
van der Heden van Noort Gerbrand J.,
Kofoed Christian,
Talavera Ormeño Cami,
el Atmioui Dris,
Mulder Monique P. C.,
Ovaa Huib
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201809232
Subject(s) - proteases , enzyme , ubiquitin , chemistry , computational biology , biochemistry , deubiquitinating enzyme , in vivo , nanotechnology , microbiology and biotechnology , biology , genetics , materials science , gene
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.