Controlled Self-Assembly of the Catalytic Core of Hydrolases Using DNA Scaffolds

Precisely organizing functional molecules of the catalytic cores in natural enzymes to promote catalytic performance is a challenging goal in respect to artificial enzyme construction. In this work, we report a DNA-scaffolded mimicry of the catalytic cores of hydrolases, which showed a controllable and hierarchical acceleration of the hydrolysis of fluorescein diacetate (FDA). The results revealed that the efficiency of hydrolysis was greatly increased by the DNA-scaffold-induced proximity of catalytic amino acid residues (histidine and arginine) with up to 4-fold improvement relative to the free amino acids. In addition, DNA-scaffolded one-dimensional and two-dimensional assemblies of multiple catalytic cores could further accelerate the hydrolysis. This work demonstrated that the DNA-guided assembly could be used as a promising platform to build enzyme mimics in a programmable and hierarchical way.