Cramer Evan R, Starcovic Sarah A, Avey Rebekah M, Kaya Ali I, Robart Aaron R
Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, WV, 20506, USA.
NE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, IL, 60439, USA.
Commun Chem. 2023 Jun 10;6(1):119. doi: 10.1038/s42004-023-00924-3.
Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA-cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10-23 DNAzyme. Here, we report a 2.7 Å crystal structure of the RNA-cleaving 10-23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10-23 DNAzyme.
脱氧核酶（DNAzyme）是能够催化化学反应的体外进化DNA序列。切割RNA的10-23脱氧核酶是最早进化出来的脱氧核酶，具有作为生物传感器和敲低剂的临床和生物技术应用。脱氧核酶不需要募集其他成分来切割RNA并且可以周转，因此它们相对于其他敲低方法（siRNA、CRISPR、吗啉代）具有明显优势。尽管如此，缺乏结构和机制信息阻碍了10-23脱氧核酶的优化和应用。在这里，我们报道了处于同二聚体构象的切割RNA的10-23脱氧核酶的2.7埃晶体结构。虽然观察到脱氧核酶与底物的适当配位以及结合镁离子的有趣模式，但二聚体构象可能并未捕捉到10-23脱氧核酶的真正催化形式。
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