脱氧核酶
血红素
拓扑(电路)
G-四倍体
DNA
化学
反平行(数学)
霍利迪路口
组合化学
酶
生物化学
血红素
DNA修复
物理
数学
组合数学
量子力学
磁场
作者
Dehui Qiu,Ming Cheng,Petr Stadlbauer,Jielin Chen,Michal Langer,Xiaobo Zhang,Qiang Gao,Huangxian Ju,Jiřı́ Šponer,Jean‐Louis Mergny,David Monchaud,Jun Zhou
标识
DOI:10.1021/acscatal.3c02818
摘要
The nature, composition, and topology of the active sites of both natural and artificial enzymes are key determinants of their catalytic performance. While interesting structural insights have been obtained for natural enzymes (e.g., horseradish peroxidase, HRP), the accurate catalytic microenvironment of HRP-mimicking DNA-based catalysts known as G-quadruplex (GQ)/hemin DNAzymes is still unclear. Herein, we report on a strategy allowing for fully controlling the nature of the active site of GQ DNAzyme, precisely manipulating the composition and topology of the hemin (Fe(III)-protoporphyrin IX) cofactor binding site. This was achieved by introducing GQ within a Holliday junction (HJ) suprastructure that enables to seize control of both the GQ folding topology (parallel, antiparallel, hybrid) and the GQ strand directionality (clockwise, counter-clockwise). By doing so, we demonstrate that the different GQ topologies are equivalent for both hemin binding and activation and that the flanking nucleotides (dA or dTC) modulate the activation of hemin in a GQ topology-dependent manner. Our experimental findings are supported by the most extensive molecular dynamics simulations ever been done on GQ DNAzyme, thus providing unique mechanistic insights into the biocatalytic activity of GQs.
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