Harnessing Ionic Selectivity in Acetyltransferase Chemoproteomic Probes.

ABSTRACT: Chemical proteomics provides a powerful strategy for the high-throughput assignment of enzyme function or inhibitor selectivity. However, identifying optimized probes for an enzyme family member of interest and differentiating signal from the background remain persistent challenges in the field. To address this obstacle, here we report a physiochemical discernment strategy for optimizing chemical proteomics based on the coenzyme A (CoA) cofactor. First, we synthesize a pair of CoA-based sepharose pulldown resins differentiated by a single negatively charged residue and find this change alters their capture properties in gel-based profiling experiments. Next, we integrate these probes with quantitative proteomics and benchmark analysis of "probe selectivity" versus traditional "competitive

SUBMITTER: Jing Y 

PROVIDER: S-EPMC9093059 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature