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Issue 23, 2019
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Probing and regulating the activity of cellular enzymes by using DNA tetrahedron nanostructures

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Abstract

Given the essential role of apurinic/apyrimidinic endonuclease (APE1) in gene repair and cancer progression, we report a novel approach for probing and regulating cellular APE1 activity by using DNA tetrahedrons. The tetrahedron with an AP site-containing antenna exhibits high sensitivity and specificity to APE1. It is suitable for APE1 in vitro detection (detection limit 5 pM) and cellular fluorescence imaging without any auxiliary transfection reagents, which discriminates the APE1 expression level of cancer cells and normal cells. In contrast, the tetrahedron with an AP site on its scaffold exhibits high binding affinity to APE1 but limits enzymatic catalysis making this nanostructure an APE1 inhibitor with an IC50 of 14.8 nM. It suppresses the APE1 activity in living cells and sensitizes cancer cells to anticancer drugs. We also demonstrate that the APE1 probe and inhibitor can be switched allosterically via stand displacement, which holds potential for reversible inhibition of APE1. Our approach provides a new way for fabricating enzyme probes and regulators and new insights into enzyme–substrate interactions, and it can be expanded to regulate other nucleic acid related enzymes.

Graphical abstract: Probing and regulating the activity of cellular enzymes by using DNA tetrahedron nanostructures

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Supplementary files

Article information


Submitted
18 Apr 2019
Accepted
03 May 2019
First published
06 May 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 5959-5966
Article type
Edge Article

Probing and regulating the activity of cellular enzymes by using DNA tetrahedron nanostructures

Y. Zhang, Y. Deng, C. Wang, L. Li, L. Xu, Y. Yu and X. Su, Chem. Sci., 2019, 10, 5959
DOI: 10.1039/C9SC01912J

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