Advances in Activity-Based Protein Profiling of Functional Tyrosines in Proteomes

Activity-based protein profiling (ABPP) is a chemical proteomic method for investigating functional states of proteins in native biological settings. By quantifying changes in probe binding states of active and regulatory protein sites, ABPP reveals functional information on protein regulation and can be configured in competitive settings to determine global selectivity profiles of tool compounds and drugs in lysates, cells, and animals. Chemical probes used for ABPP analyses can target protein families with conserved enzymatic or structural features or can broadly profile the proteome using electrophiles with reactivity towards functional groups on amino acid side chains. The latter approach has provided insights to protein sites involved in allosteric regulation and non-enzymatic functions. This review introduces quantitative ABPP workflows and discusses electrophilic groups used for ABPP profiling of functional sites in the proteome with an emphasis on tyrosine residues.