In this thesis we investigated the molecular mechanism of a subset of USPs (Ubiquitin-Specific Proteases), a class of deubiquitinating enzymes. Our findings describe how USP7, one of the subset members, can get activated by its biological target, sketching a role for its biological partner proteins. Furthermore, we describe on a molecular level how the domain structure of USP7, but also the paralogue USP40, aids in the intrinsic activity by activating the enzyme. We show that this self-activation is a conserved mechanism, yielding valuable information for the development of inhibitory molecules, but altogether also providing insight into the biological workings and role of these USP enzymes.

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Keywords USP7, Ubiquitin, protease, enzymatic activity, structural biology, biochemistry, biophysical analysis, activity mechanism, protein
Promotor T.K. Sixma (Titia) , A. Perrakis (Anastassis)
Publisher Erasmus University Rotterdam
ISBN 978-94-6380-188-1
Persistent URL
Note For copyright reasons there is a partial embargo for this dissertation
Kim, R.Q. (2019, March 8). Structural and Mechanistic Studies on Deubiquitinating Enzymes USP7 and USP40. Erasmus University Rotterdam. Retrieved from