Non-canonical DNA-junction structures are important in human disease and nucleic acid nanoscience and there is a growing interest in how to bind and modulate them. A key next step is to exert 'on command' control over such binding. Herein we develop a new metallo-supramolecular triple-helicate cylinder agent that is inert to DNA junction binding until activated by human enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and its cofactor nicotinamide adenine dinucleotide phosphate (NADPH). This inactive cylinder bears six flexible arms each with a quinone group at the termini. Reduction by the enzyme leads to all six arms being removed, transforming the inert cylinder into a new and active metallo-supramolecular agent that binds junctions. This gives the ability to 'switch-on' DNA junction formation and binding in response to the presence of two external stimuli - a human enzyme overexpressed in many disease states, and NADPH - and absence of inhibitor, giving NAND logic control. Modelling indicates the binding activation originates not in steric unblocking but changes in conformational flexibility. The work provides the foundation for and a route map towards future designs of sophisticated, inert, supramolecular structures which are transformed by enzymes into new, active, supramolecular structures for a variety of potential applications.