Structural characterization of a carbon monoxide adduct of a heme–DNA complex

• Published in: Journal of biological inorganic chemistry 2012-03, Vol.17 (3), p.437-445
• Main Authors: Saito, Kaori, Tai, Hulin, Fukaya, Masashi, Shibata, Tomokazu, Nishimura, Ryu, Neya, Saburo, Yamamoto, Yasuhiko
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Carbon Monoxide - chemistry; DNA - chemistry; G-Quadruplexes; Heme - chemistry; Humans; Life Sciences; Magnetic Resonance Spectroscopy; Microbiology; Models, Molecular; Molecular Structure; Original Paper; Quantum Theory
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-011-0866-8

The structure of a carbon monoxide (CO) adduct of a complex between heme and a parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), has been characterized using 1 H and 13 C NMR spectroscopy and density function theory calculations. The study revealed that the heme binds to the 3′-terminal G-quartet of the DNA though a π – π stacking interaction between the porphyrin moiety of the heme and the G-quartet. The π – π stacking interaction between the pseudo- C 2 -symmetric heme and the C 4 -symmetric G-quartet in the complex resulted in the formation of two isomers possessing heme orientations differing by 180° rotation about the pseudo- C 2 axis with respect to the DNA. These two slowly interconverting heme orientational isomers were formed in a ratio of approximately 1:1, reflecting that their thermodynamic stabilities are identical. Exogenous CO is coordinated to heme Fe on the side of the heme opposite the G-quartet in the complex, and the nature of the Fe–CO bond in the complex is similar to that of the Fe–CO bonds in hemoproteins. These findings provide novel insights for the design of novel DNA enzymes possessing metalloporphyrins as prosthetic groups. Graphical abstract