An in vitro Forster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9.

ABSTRACT: SUMOylation is one of the posttranslational modifications that mediate cellular activities such as transcription, DNA repair, and signal transduction and is involved in the cell cycle. However, only a limited number of small molecule inhibitors have been identified to study its role in cellular processes. Here, we report a Förster resonance energy transfer (FRET) high-throughput screening assay based on the interaction between E2 Ubc9 and E3 PIAS1. Of the 3200 compounds screened, 34 (1.1%) showed higher than 50% inhibition and 4 displayed dose-response inhibitory effects. By combining this method with a label-free surface plasmon resonance (SPR) assay, false positives were excluded leading to discovering WNN0605-F008 and WNN1062-D002 that bound to Ubc9 with K_D values of 1.93 ± 0

SUBMITTER: Wang YZ 

PROVIDER: S-EPMC7656853 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature