Extended Data Fig. 10: A common DUB ligandability hotspot and a shared hotspot anchor.

a-d, Chemical and structural representations of inhibitors of USP7 (a, b), USP14 (c) and USP28 (d). Shown are the overlays of the inhibitor-bound structures with ubiquitin-bound structures of the respective DUBs (first box) and the inhibitor-bound structures of each DUB overlaid on NK036 bound structure of USP30 (second box). Highlighted is the close-up view of the compound binding site at the ubiquitin Leu73 pocket. Please note the chemically related hotspot anchors in b and c. Structural superpositions were aligned taking only the protein residues into account. The chemical moieties of the inhibitors that occupy the Leu73 pocket are highlighted with orange background.