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

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 H-1 and C-13 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 pi-pi stacking interaction between the porphyrin moiety of the heme and the G-quartet. The pi-pi 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 180A degrees 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.