Shape-Dependent Biomimetic Inhibition of Enzyme by Nanoparticles and Their Antibacterial Activity.

Enzyme inhibitors are ubiquitous in all living systems, and their biological inhibitory activity is strongly dependent on their molecular shape. Here, we show that small zinc oxide nanoparticles (ZnO NPs)-pyramids, plates, and spheres-possess the ability to inhibit activity of a typical enzyme β-galactosidase (GAL) in a biomimetic fashion. Enzyme inhibition by ZnO NPs is reversible and follows classical Michaelis-Menten kinetics with parameters strongly dependent on their geometry. Diverse spectroscopic, biochemical, and computational experimental data indicate that association of GAL with specific ZnO NP geometries interferes with conformational reorganization of the enzyme necessary for its catalytic activity. The strongest inhibition was observed for ZnO nanopyramids and compares favorably to that of the best natural GAL inhibitors while being resistant to proteases. Besides the fundamental significance of this biomimetic function of anisotropic NPs, their capacity to serve as degradation-resistant enzyme inhibitors is technologically attractive and is substantiated by strong shape-specific antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), endemic for most hospitals in the world.

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