Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study.
Genome sequencing projects have uncovered thousands of uncharacterized enzymes in eukaryotic and prokaryotic organisms. Deciphering the physiological functions of enzymes requires tools to profile and perturb their activities in native biological systems. Activity-based protein profiling has emerged as a powerful chemoproteomic strategy to achieve these objectives through the use of chemical probes that target large swaths of enzymes that share active-site features. Here, we review activity-based protein profiling and its implementation to annotate the enzymatic proteome, with particular attention given to probes that target serine hydrolases, a diverse superfamily of enzymes replete with many uncharacterized members.
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
Gabriel M
GM
Simon
Benjamin F
BF
Cravatt
D000818:Animals; D001671:Biochemistry / Q000379:methods; D002384:Catalysis; D020134:Catalytic Domain; D004798:Enzymes / Q000737:chemistry; D016678:Genome; D006801:Humans; D006867:Hydrolases / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D012694:Serine / Q000737:chemistry*
D004798:Enzymes; D063065:Organophosphonates; D020543:Proteome; D012694:Serine; D006867:Hydrolases; D010447:Peptide Hydrolases