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Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes.

A recent paper in Nature Communications describes a collaborative effort between scientists at UbiQ, Genentech, Boston Biochem (Bio-Techne) and Stanford University (1).

Here a reactive-site-centric chemoproteomics protocol is presented which allows evaluating activity and probe reactivity of deubiquitinating enzymes (DUBs, also termed deubiquitylases). The chemoproteomics protocol makes use of a new type of bio-orthogonally tagged activity-based probe (ABP) and sequential on-bead digestions to enhance the identification of probe-labeling sites on DUBs. Ultimately, ZUFSP (ZUP1) was identified as a previously unannotated DUB with high selectivity toward cleaving K63-linked ubiquitin chains (3-5).

 

(1) Hewings et al. Nature Communications 2018, 9, 1162. https://www.nature.com/articles/s41467-018-03511-6

Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes
David S. Hewings, Johanna Heideker, Taylur P. Ma, Andrew P. AhYoung, Farid El Oualid, Alessia Amore, Gregory T. Costakes, Daniel Kirchhofer, Bradley Brasher, Thomas Pillow, Nataliya Popovych, Till Maurer, Carsten Schwerdtfeger, William F. Forrest, Kebing Yu, John Flygare, Matthew Bogyo & Ingrid E. Wertz

Hewings, D.S., Heideker, J., Ma, T.P. et al. Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes. Nat Commun 9, 1162 (2018). https://doi.org/10.1038/s41467-018-03511-6

(2) El Oualid et al. 2010, 49, 10149. https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201005995
(3) Kwasna et al. Molecular Cell 2018, 70, 150. https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30142-4
(4) Haahr et al. Molecular Cell 2018, 70, 165. https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30143-6
(5) Hermanns et al. Nature Communications 2018, 9, 799. https://www.nature.com/articles/s41467-018-03148-5