Pyridoxal 5’phosphate (PLP) is an essential cofactor for enzymes that catalyze diverse reactions in central metabolism. 2-aminoacrylate (2AA) is a reactive enamine and an obligate catalytic intermediate in some PLP-mediated reactions. In the absence of the enamine/imine deaminase RidA, Salmonella enterica accumulates 2AA, which causes cellular stress. 2AA can attack PLP in the active site of some enzymes and covalently inactivate the enzyme by forming a PLP/pyruvate adduct. Damage to a few target enzymes has been characterized in vivo and in vitro. The mechanism of 2AA attack suggests the majority of the cellular PLP-DEs would be targets of 2AA damage. Herein a chemical proteomics workflow that uses PL (pyridoxal) probes to enrich PLP-DEs with a click chemistry-based protocol was implemented to investigate the global scale of 2AA damage in S. enterica. Results showed PLP-DEs in S. enterica could be enriched when cells were labeled with two different PL probes. Labeling cells by providing the PL probe as the sole source of vitamin B6 found several proteins that were enriched when grown in conditions of high 2AA versus low 2AA stress. These data identified proteins previously shown to be attacked by 2AA and identified new candidate targets, showing this approach will contribute to continuing efforts to define the 2AA stress response with a global perspective. Growth analyses indicated 2AA stress impacts the salvage of PL probes, suggesting these and other PL probes will be valuable in future physiological studies to understand PLP salvage, a critical pathway in all organisms. In total, this study expands our understanding of 2AA metabolism and takes an initial step toward characterizing the global impact of 2AA stress in S. enterica.