Activity-Based Protein Profiling of Oxidases and Reductases

Abstract

Activity-based protein profiling (ABPP) as a proteomic tool allows measuring the activity of enzyme classes or distinct proteins in their cellular context, annotating the function of uncharacterized proteins, and investigating the target profile of small molecule inhibitors. While hydrolases and other enzyme classes, which exhibit a characteristic nucleophilic residue, can be addressed by electrophilic activity-based probes, the large enzyme class of oxidoreductases has received much less attention in ABPP. In this review the state of the art of ABPP of oxidases is presented. The most frequent principle in ABPP for oxidases is the oxidative activation of the ABPP probe leading to an electrophilic group as exemplified for alkyne or amine based warheads. Alternatively, in rare cases ABPP probes can address characteristic electrophilic or nucleophilic residues of certain oxidases. Most recently, with NQO2 the first example of ABPP for a reductase has been reported.