Promiscuity and electrostatic flexibility in the alkaline phosphatase superfamily

- Enzyme promiscuity is widespread and important for the evolution of enzyme function.
- Alkaline phosphatases (APs) are a model system for understanding enzyme promiscuity.
- Computational studies provide significant insight into AP activity and promiscuity.
- APs select between transition states primarily on the basis of charge distribution.
- Electrostatic cooperativity is a key driving force for AP functional evolution.