Bio-Zombie: the rise of pseudoenzymes in biology

Pseudoenzymes are catalytically dead counterparts of enzymes. Despite their first description some 50 years ago, the importance and functional diversity of these ‘fit-for-purpose’ polypeptides is only now being appreciated. Pseudoenzymes have been identified throughout all the kingdoms of life and, owing to predicted deficits in enzyme activity due to the absence of catalytic residues, have been variously referred to as pseudoenzymes, non-enzymes, dead enzymes, prozymes or ‘zombie’ proteins. An important goal of the recent Biochemical Society Pseudoenzymes-focused meeting was to explore the functional and evolutionary diversity of pseudoenzymes and to begin to evaluate their functions in biology, including cell signalling and metabolism. Here, we summarise the impressive breadth of enzyme classes that are known to have pseudoenzyme counterparts and present examples of known cellular functions. We predict that the next decades will represent golden years for the analysis of pseudoenzymes.