Characterization of Heme鈥揇NA Complexes Composed of Some Chemically Modified Hemes and Parallel G-Quadruplex DNAs

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• 作者：Yasuhiko Yamamoto ; Masashi Kinoshita ; Yuya Katahira ; Haruna Shimizu ; Yue Di ; Tomokazu Shibata ; Hulin Tai ; Akihiro Suzuki ; Saburo Neya
• 刊名：Biochemistry
• 出版年：2015
• 出版时间：December 15, 2015
• 年：2015
• 卷：54
• 期：49
• 页码：7168-7177
• 全文大小：505K
• ISSN：1520-4995

文摘

Heme {Fe(II)- or Fe(III)-protoporphyrin IX complex [heme(Fe²⁺) or heme(Fe³⁺), respectively]} binds selectively to the 3鈥?terminal G-quartet of a parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), through a 蟺鈥撓€ stacking interaction between the porphyrin moiety of the heme and the G-quartet. The binding affinities of some chemically modified hemes(Fe³⁺) for DNA and the structures of complexes between the modified hemes(Fe²⁺) and DNA, with carbon monoxide (CO) coordinated to the heme Fe atom on the side of the heme opposite the G6 G-quartet, have been characterized to elucidate the interaction between the heme and G-quartet in the complexes through analysis of the effects of the heme modification on the structural properties of the complex. The study revealed that the binding affinities and structures of the complexes were barely affected by the heme modification performed in the study. Such plasticity in the binding of heme to the G-quartet is useful for the versatile design of the complex through heme chemical modification and DNA sequence alteration. Furthermore, exchangeable proton signals exhibiting two-proton intensity were observed at approximately 鈭?.5 ppm in the ¹H nuclear magnetic resonance (NMR) spectra of the CO adducts of the complexes. Through analysis of the NMR results, together with theoretical consideration, we concluded that the heme(Fe²⁺) axial ligand trans to CO in the complex is a water molecule (H₂O). Identification of the Fe-bound H₂O accommodated between the heme and G-quartet planes in the complex provides new insights into the structure鈥揻unction relationship of the complex.