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Issue 44, 2019
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Development of a DUB-selective fluorogenic substrate

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Abstract

Ubiquitination is a post-translational modification that is involved in a plethora of cellular processes. Target proteins can be specifically modified with a single ubiquitin (Ub) molecule or with complex chains. In recent years, research has focused on deubiquitinating enzymes (DUBs) as potential therapeutic candidates in various diseases. USP16 is an emerging target due to its involvement in mitosis and stem cell self-renewal. Generally, activity-based probes (ABPs) used to study DUBs are based on the ubiquitin scaffold, thus lacking target selectivity. To overcome this issue, we designed a Ub-based activity probe bearing specific mutations to achieve selectivity for USP16, by combining structural modelling and analysis and mutational calculation predictions. We develop a fluorogenic substrate, the first of its kind, that is processed exclusively by USP16, which allows us to monitor USP16 activity in complex samples.

Graphical abstract: Development of a DUB-selective fluorogenic substrate

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Publication details

The article was received on 07 May 2019, accepted on 28 Sep 2019 and first published on 30 Sep 2019


Article type: Edge Article
DOI: 10.1039/C9SC02226K
Chem. Sci., 2019,10, 10290-10296
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Development of a DUB-selective fluorogenic substrate

    L. Gjonaj, A. Sapmaz, D. Flierman, G. M. C. Janssen, P. A. van Veelen and H. Ovaa, Chem. Sci., 2019, 10, 10290
    DOI: 10.1039/C9SC02226K

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