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

Katharina F. Witting; Gerbrand J. Van Der Heden Van Noort; Christian Kofoed; Cami Talavera Ormeño; Dris El Atmioui; Monique P. C. Mulder; Huib Ovaa

doi:10.1002/anie.201809232

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

Katharina F. Witting, Gerbrand J. Van Der Heden Van Noort, Christian Kofoed, Cami Talavera Ormeño, Dris El Atmioui, Monique P. C. Mulder, Huib Ovaa

Department of Chemistry

12 Citations (Scopus)

27 Downloads (Pure)

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.

Original language	English
Journal	Angewandte Chemie International Edition
Volume	57
Issue number	43
Pages (from-to)	14164-14168
Number of pages	5
ISSN	1433-7851
DOIs	https://doi.org/10.1002/anie.201809232
Publication status	Published - 22 Oct 2018

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title = "Generation of the UFM1 Toolkit for Profiling UFM1-Specific Proteases and Ligases",

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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AU - Witting, Katharina F.

AU - Van Der Heden Van Noort, Gerbrand J.

AU - Kofoed, Christian

AU - Talavera Ormeño, Cami

AU - El Atmioui, Dris

AU - Mulder, Monique P. C.

AU - Ovaa, Huib

PY - 2018/10/22

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N2 - 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.

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

Abstract

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