Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.
Metallomics. 2018 Jan 24;10(1):30-48. doi: 10.1039/c7mt00268h.
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 Ca 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.
核酸酶（NAEs）是具有催化活性的 RNA 和 DNA 分子。具有 RNA 切割活性的 NAE 因其在分析化学、基因治疗和纳米技术中的应用而得到广泛研究。大多数 NAE 活性需要金属离子。从生化角度来看，这些 NAE 让人想起具有金属结合位点的金属蛋白酶。虽然大多数 NAE 反应只需要一种金属，但越来越多的最新例子表明，反应需要两种甚至三种金属。由于协同作用，如果这些 NAE 使用相同的金属离子，其金属结合谱就会更加明显。详细的研究表明了镧系元素和 Ca 结合 DNA 酶的例子，其中金属与可切割磷酸酯的非桥氧原子相互作用，这些 DNA 酶通常具有很强的硫效应，不能通过添加硫亲金属来挽救。另一种类型使用多种不同的金属，其中一种金属与可切割磷酸酯相互作用，另一种金属与催化环结合以进行变构相互作用。这种变构 NAE 也可以通过基于现有 NAE 的合理设计或有目的选择来获得。这些多金属 NAE 可以用作金属离子作为输入的逻辑门。在本文中，我们根据它们对金属离子的使用情况综述了不同类型的 NAE。综述的 NAE 包括核酶、DNA 酶和合理设计的适体酶。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。
