Activity-based probes are widely used to monitor the activity of enzyme families in biological systems.  Inferring enzyme activity from probe reactivity requires that the probe reacts with the enzyme on its active site; however, the sites of probe labeling are rarely determined.  Here we describe the design of bi-specific deubiquitinase probes and the development of an enhanced chemoproteomic approach to study the activity of deubiquitinases.  This approach identifies probe labeling sites, revealing that several deubiquitinases react with activity-based probes away from the protease active site. Furthermore we use this method to identify a member of a structurally distinct class of deubiquitinase enzymes.

Reactive site-centric chemoproteomics identifies a new class of deubiquitinase enzymes

255th National Meeting (2018)

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