Structure-activity relationship of pseudoknot-type hammerhead ribozyme reveals key structural elements for enhanced catalytic activity
Structure-activity relationship of pseudoknot-type hammerhead ribozyme reveals key structural elements for enhanced catalytic activity
复制标题
假结型锤头核酶的构效关系揭示了增强催化活性的关键结构元件
DOI：
10.1080/15257770.2019.1669169
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Tanaka Yoshiyuki
中科院分区：
文献类型：
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作者：
Yamada Mituhiro;Tanaka Yoshiyuki
已知假结型锤头状核酶（PK-HHRz）通过环I和环II之间的假结相互作用被激活。为了通过假结形成获得最大活化，我们研究了PK-HHRz的构效关系。通过这些研究，PK-HHRz切割反应的结构要求得到了明确的定义。此外，我们发现了一个PK-HHRz具有更高的切割活性比野生型序列。虽然修饰通常会破坏酶的活性，但在这种情况下，环II的延长增加了PK-HHRz的活性。这些新发现将为设计用于基因治疗/操纵剂和生物化学/纳米技术工具的PK-HHRz变体提供结构基础。
The pseudoknot-type hammerhead ribozyme (PK-HHRz) is known to be activated by a pseudoknot interaction between loops I and II. To obtain maximal activation through the pseudoknot formation, we studied the structure–activity relationship of PK-HHRz. From these studies, the structural requirements of the PK-HHRz cleavage reaction were clearly defined. In addition, we discovered a PK-HHRz with higher cleavage activity than the wild-type sequence. Although modifications generally disrupt the activity of enzymes, in this case the elongation of loop II increased the activity of PK-HHRz. These new findings will form a structural basis for designing PK-HHRz variants for gene-therapeutic/manipulating agents and biochemical/nanotechnological tools.