The enzyme nomenclature system, commonly known as the enzyme commission (EC) number, plays a key role in classifying and predicting enzymatic reactions. However, numerous reactions have been described in various pathways that do not have an official EC number, and the reactions are not expected to have an EC number assigned because of a lack of articles published on enzyme assays. To predict the EC number of a non-classified enzymatic reaction, we focus on the structural similarity of its substrate and product to the substrate and product of reactions that have been classified.