Computational Protein Redesign

The image to the left shows p-nitrophenyl phosphate bound to the active site of Pseudomonas aeruginosa arylsulfatase, a native sulfatase capable of catalyzing a range of phosphorus-based substrates. Such catalytic promiscuity is being observed for an ever increasing number of systems, leading to the possibility that most (if not all) enzymes are to some degree promiscuous. Understanding how enzymes are able to catalyze substrates with vastly different requirements for efficient catalysis is a cornerstone to being able to understand evolution of function within enzyme superfamilies, which in turn can be used to develop artificial enzymes with far greater catalytic proficiencies than the current generation of designer enzymes.