Identifying USP1 Inhibitors with Allosteric Effect on Its Triple Catalytic Center through Virtual Screening

Figure 1

(a)The trimeric complex of USP1-ubiquitin-ML323, wherein the yellow color represents ubiquitin, white cartoon represents USP1, blue sticks represent ML323, and pink represents the catalytic center (b). The conformational changes in the catalytic center with and without the inhibitor ML323 are depicted, with hydrogen bonds shown as dashed lines and nucleophilic attack represented by a solid arrow. (c) The binding mode of ML323 is illustrated, with yellow dotted lines indicating hydrogen bonding and green dotted lines representing Pi-Pi conjugation. (d) The pharmacophore model “ARRRA.”