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.
Department of Chemical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.|Department of Chemical Engineering, Kyonggi University , Suwon 443-760, South Korea.
Sang-Ho
SH
Cha
Biointerfaces Institute, University of Michigan , Ann Arbor, Michigan48109, United States.|China Pharmaceutical University , 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, China.
Jin
J
Hong
Biointerfaces Institute, University of Michigan , Ann Arbor, Michigan48109, United States.|Department of Emergency Medicine, University of Michigan , Ann Arbor, Michigan 48109, United States.
Matt
M
McGuffie
Department of Chemical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.|Biointerfaces Institute, University of Michigan , Ann Arbor, Michigan48109, United States.|Department of Chemical Engineering, Myongji University , Yongin 449-728, South Korea.
Bongjun
B
Yeom
Biointerfaces Institute, University of Michigan , Ann Arbor, Michigan48109, United States.|Department of Emergency Medicine, University of Michigan , Ann Arbor, Michigan 48109, United States.
J Scott
JS
VanEpps
Department of Chemical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.|Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.|Biointerfaces Institute, University of Michigan , Ann Arbor, Michigan48109, United States.|Department of Materials Science and Engineering, University of Michigan , Ann Arbor, Michigan 48198, United States.
Nicholas A
NA
Kotov
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D032701:Biomimetics; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D014961:X-Ray Diffraction; D015034:Zinc Oxide / Q000737:chemistry; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D001616:beta-Galactosidase; D015034:Zinc Oxide
MRSA; ZnO; bacteria; enzymes; inhibitors; nanoparticles; reaction kinetics; zinc oxide