Nucleic acid enzymes (NAEs) are catalytically active RNA and DNA molecules. NAEs with RNA-cleaving activity are most extensively studied for applications in analytical chemistry, gene therapy and nanotechnology. Most NAEs require metal ions for activity. From a biochemical standpoint, these NAEs are reminiscent of metalloprotein enzymes with metal binding sites. While most NAEs require a single metal for the reaction, more and more recent examples have emerged that use two or even three metals for the reaction. The metal binding profile is sharper for these NAEs if they use the same metal ion due to cooperativity. Detailed studies have indicated examples of lanthanide and Ca²⁺ binding DNAzymes, where the metals interact with the non-bridging oxygen atoms in the scissile phosphate, and these DNAzymes often have a very strong thio effect that cannot be rescued by adding thiophilic metals. Another type uses multiple different metals, where one metal interacts with the scissile phosphate and the other binds to the catalytic loop for allosteric interactions. Such allosteric NAEs can also be obtained via rational design or intentional selection based on existing NAEs. These multi-metal NAEs might be useful as logic gates with metal ions as inputs. In this article, we review different types of NAEs based on their use of metal ions. The NAEs reviewed include ribozymes, DNAzymes and rationally designed aptazymes. Finally, their emerging applications are discussed, and some future research opportunities are proposed.

中文翻译：

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多金属依赖性核酸酶

核酸酶（NAE）是具有催化活性的RNA和DNA分子。具有RNA裂解活性的NAE在分析化学，基因治疗和纳米技术中的应用得到了最广泛的研究。大多数NAE都需要金属离子才能发挥作用。从生物化学的角度来看，这些NAE让人想起具有金属结合位点的金属蛋白酶。尽管大多数NAE都需要一种金属来进行反应，但越来越多的示例使用了两种甚至三种金属来进行反应。如果这些NAE由于协同作用而使用相同的金属离子，则它们的金属结合曲线会更锐利。详细的研究表明了镧系元素和Ca ^2+的实例结合脱氧核糖核酸酶，其中金属与可裂解的磷酸盐中的非桥接氧原子相互作用，并且这些脱氧核糖核酸酶通常具有非常强的硫代作用，而无法通过添加亲硫金属来挽救。另一种类型使用多种不同的金属，其中一种金属与易裂磷酸盐相互作用，而另一种则与催化环结合以实现变构相互作用。这样的变构NAE也可以通过基于现有NAE的合理设计或有意选择。这些多金属NAE可用作金属离子作为输入的逻辑门。在本文中，我们根据金属离子的使用情况来审查不同类型的NAE。审查的NAE包括核酶，DNA酶和合理设计的核酶。最后，讨论了它们的新兴应用，并提出了一些未来的研究机会。