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.

Additional Metadata
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 hdl.handle.net/1765/115598
Note For copyright reasons there is a partial embargo for this dissertation
Citation
Kim, R.Q. (2019, March 8). Structural and Mechanistic Studies on Deubiquitinating Enzymes USP7 and USP40. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/115598