In order to render proteins responsive to light, we are incorporating a single photocaging group at a defined amino acid residue that is crucial for protein activity. This residue is identified based on mechanistic data that has been reported in the literature or generated by us. Alternatively, sites are selected based on structural information that allows us to generate hypotheses regarding the impact that a caging group would have on protein activity. For example, we have optochemically controlled the function of T7 RNA polymerase, Taq DNA polymerase, Cre recombinase, and the kinase MEK1, by blocking an essential active site tyrosine or lysine residue with a photocaging group. Importantly, the enzymes were completely inactive until illumination with UV light removed the caging groups.