Enzyme promiscuity, a property with practical applications in biotechnology and synthetic biology, has been related to the evolvability of enzymes. At the molecular level, several structural mechanisms have been linked to enzyme promiscuity in enzyme families. However, it is at present unclear to what extent these observations can be generalized. Here, we introduce for the first time a method for predicting catalytic and substrate promiscuity using a graph-based representation known as molecular signature.