血红素与所有平行链单体G-四链体DNA配合物的结构和催化活性,Biochemistry

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血红素与所有平行链单体G-四链体DNA配合物的结构和催化活性
Biochemistry ( IF 2.9 ) Pub Date : 2018-09-20 00:00:00 , DOI: 10.1021/acs.biochem.8b00792
Yasuhiko Yamamoto _{1,

2,

3} , Haruka Araki ₁ , Ryosuke Shinomiya ₁ , Kosuke Hayasaka ₁ , Yusaku Nakayama ₁ , Kentaro Ochi ₁ , Tomokazu Shibata ₁ , Atsuya Momotake ₁ , Takako Ohyama ₄ , Masaki Hagihara ₅ , Hikaru Hemmi ₆

Affiliation

处于亚铁和三价铁状态的血红素[分别为血红素（Fe ²⁺）和血红素（Fe ³⁺）]与肌苷形成的所有平行链单体G-四链体DNA的3'-末端G四联体选择性结合（I ）的序列，即d（TAGGGTGGGTTTTGGGGTGIG）DNA（18mer）和d（TAGGGTGGGTTGGGTGIGA）DNA（18mer / A），通过血红素的卟啉部分和G四联体之间的π–π堆积相互作用形成1 ：1复合物[分别是血红素-DNA（18mer）和血红素-DNA（18mer / A）复合物]。与单独的血红素（Fe ³⁺）相比，这些复合物显示出增强的过氧化物酶活性，并且血红素（Fe ³⁺）–DNA（18mer / A）复合物的活性大于血红素（Fe ^3+））-DNA（18mer）1，表示DNA序列的3'-末端A充当酸碱催化剂，促进了催化反应。在络合物中，血红素和G四元体之间的界面处的水分子（H ₂ O）作为轴向配体与血红素Fe原子配位，并可能充当供电子配体，从而促进氢的过氧化氢键裂解。过氧化物结合于血红素铁原子，反式为H ₂ O，用于活性物质的产生。血红素中观察到的分子间核Overhauser效应，DNA，和Fe-粘合的H ₂ ○表示，在H _2个关于H 2 O旋转₂配合物中血红素和DNA的O-Fe配位键。因此，该配合物中的H ₂ O不仅在其电子性质方面而且在其动态性质方面都是独特的。这些发现为血红素-脱氧核酶和-核酶的设计提供了新颖的见解。

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Structures and Catalytic Activities of Complexes between Heme and All Parallel-Stranded Monomeric G-Quadruplex DNAs

Heme in its ferrous and ferric states [heme(Fe²⁺) and heme(Fe³⁺), respectively] binds selectively to the 3′-terminal G-quartet of all parallel-stranded monomeric G-quadruplex DNAs formed from inosine(I)-containing sequences, i.e., d(TAGGGTGGGTTGGGTGIG) DNA(18mer) and d(TAGGGTGGGTTGGGTGIGA) DNA(18mer/A), through a π–π stacking interaction between the porphyrin moiety of the heme and the G-quartet, to form 1:1 complexes [heme–DNA(18mer) and heme–DNA(18mer/A) complexes, respectively]. These complexes exhibited enhanced peroxidase activities, compared with that of heme(Fe³⁺) alone, and the activity of the heme(Fe³⁺)–DNA(18mer/A) complex was greater than that of the heme(Fe³⁺)–DNA(18mer) one, indicating that the 3′-terminal A of the DNA sequence acts as an acid–base catalyst that promotes the catalytic reaction. In the complexes, a water molecule (H₂O) at the interface between the heme and G-quartet is coordinated to the heme Fe atom as an axial ligand and possibly acts as an electron-donating ligand that promotes heterolytic peroxide bond cleavage of hydrogen peroxide bound to the heme Fe atom, trans to the H₂O, for the generation of an active species. The intermolecular nuclear Overhauser effects observed among heme, DNA, and Fe-bound H₂O indicated that the H₂O rotates about the H₂O–Fe coordination bond with respect to both the heme and DNA in the complex. Thus, the H₂O in the complex is unique in terms of not only its electronic properties but also its dynamic ones. These findings provide novel insights into the design of heme–deoxyribozymes and −ribozymes.

更新日期：2018-09-20

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