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Authors Thomas SE, Comer J, Kim MJ, Marroquin S, Murthy V, Ramani M, Hopke TG, McCall J, Choi SO, DeLong RK
Received 21 September 2017
Accepted for publication 17 March 2018
Published 8 August 2018 Volume 2018:13 Pages 4523—4536
DOI https://doi.org/10.2147/IJN.S152222
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Thomas J Webster
Introduction: Biomedical applications of nanoparticles (NPs) as enzyme
inhibitors have recently come to light. Oxides of metals native to the
physiological environment (eg, Fe, Zn, Mg, etc.) are of particular interest—especially
the functional consequences of their enzyme interaction.
Materials and methods: Here, Fe2O3, zinc oxide (ZnO), magnesium oxide (MgO) and nickel
oxide (NiO) NPs are compared to copper (Cu) and boron carbide (B4C) NPs. The functional impact of NP interaction to
the model enzyme luciferase is determined by 2-dimensional fluorescence
difference spectroscopy (2-D FDS) and 2-dimensional photoluminescence
difference spectroscopy (2-D PLDS). By 2-D FDS analysis, the change in maximal
intensity and in 2-D FDS area under the curve (AUC) is in the order Cu~B4C>ZnO>NiO>>Fe2O3>MgO. The
induced changes in protein conformation are confirmed by tryptic digests and
gel electrophoresis.
Results: Analysis of possible trypsin cleavage sites
suggest that cleavage mostly occurs in the range of residues 112–155 and
372–439, giving a major 45 kDa band. By 2-D PLDS, it is found that B4C NPs completely ablate bioluminescence, while Cu
and Fe2O3 NPs yield a
unique bimodal negative decay rate, -7.67×103 and -3.50×101 relative light units respectively. Cu NPs, in
particular, give a remarkable 271% change in enzyme activity. Molecular
dynamics simulations in water predicted that the surfaces of metal oxide NPs
become capped with metal hydroxide groups under physiological conditions, while
the surface of B4C becomes populated with boronic
acid or borinic acid groups. These predictions are supported by the
experimentally determined zeta potential. Thin layer chromatography patterns
further support this conception of the NP surfaces, where stabilizing
interactions were in the order ionic>polar>non-polar for the series
tested.
Conclusion: Overall the results suggest that B4C and Cu NP functional dynamics on enzyme
biochemistry are unique and should be examined further for potential
ramifications on other model, physiological or disease-relevant enzymes.
Keywords: 2-dimensional
fluorescence difference, 2-D FDS, AUC, corrected light intensity emitted,
emission wavelength, excitation wavelength, wavelength of max intensity, RLU
摘要视频链接:Functional dynamics studies
on the enzyme nano-bio interface