This landmark Nature Communications paper introduced the Catalophore technology — a method for mining structural databases using active site constellations represented as 3D point clouds. The study demonstrated the discovery of previously unknown ene-reductase activity across unrelated protein folds, establishing the proof-of-principle that led to the founding of Innophore and the development of the CavitomiX platform. The work showed that proteins sharing no detectable sequence or fold similarity can harbour identical catalytic functions, detectable only through the volumetric property fields projected into their active-site cavities.