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Crystal structure of an RNA-cleaving DNAzyme
Open accessAbstract
In addition to storage of genetic information, DNA can also catalyze various reactions. RNA-cleaving DNAzymes are the catalytic DNAs discovered the earliest, and they can cleave RNAs in a sequence-specific manner. Owing to their great potential in medical therapeutics, virus control, and gene silencing for disease treatments, RNA-cleaving DNAzymes have been extensively studied; however, the mechanistic understandings of their substrate recognition and catalysis remain elusive. Here, we report three catalytic form 8–17 DNAzyme crystal structures. 8–17 DNAzyme adopts a V-shape fold, and the Pb 2+ cofactor is bound at the pre-organized pocket. The structures with Pb 2+ and the modification at the cleavage site captured the pre-catalytic state of the RNA cleavage reaction, illustrating the unexpected Pb 2+-accelerated catalysis, intrinsic tertiary interactions, and molecular kink at the active site. Our studies reveal that DNA is capable of forming a compacted structure and that the functionality-limited bio-polymer can have a novel solution for a functional need in catalysis.
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Towards automated crystallographic structure refinement with phenix.refine
Afonine, P. V., Grosse-Kunstleve, R. W., Echols, N., Headd, J. J., Moriarty, N. W., Mustyakimov, M., Terwilliger, T. C., Urzhumtsev, A., Zwart, P. H., & Adams, P. D. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444912001308 · Cited by 5,511
Cited by
McConnell, E. M., Cozma, I., Mou, Q., Brennan, J. D., Lu, Y., & Li, Y. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00240f · Cited by 477
Lake, R. J., Yang, Z., Zhang, J., & Lu, Y. (2019) · Accounts of Chemical Research · doi:10.1021/acs.accounts.9b00419 · Cited by 281
Self-citationYang, J., Zhang, J., Xing, J., Shi, Z., Han, H., & Li, Q. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s211744 · Cited by 11
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Metadata
- Authors
- Liu, H., Yu, X., Chen, Y., Zhang, J., Wu, B., Zheng, L., Haruehanroengra, P., Wang, R., Li, S., Lin, J., Li, J., Sheng, J., Huang, Z., Ma, J., & Gan, J.
- Venue
- Nature Communications
- Published
- 2017-12-08
- Volume
- 8
- Issue
- 1
- Pages
- 2006-2006
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2771262230
- Cited by
- 211
- References
- 1
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- gold
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- Liu, H., Yu, X., Chen, Y., Zhang, J., Wu, B., Zheng, L., Haruehanroengra, P., Wang, R., Li, S., Lin, J., Li, J., Sheng, J., Huang, Z., Ma, J., & Gan, J. (2017). Crystal structure of an RNA-cleaving DNAzyme. Nature Communications. https://doi.org/10.1038/s41467-017-02203-x
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