1. NMR of paramagnetic molecules
  2. Electronic manipulation of functional properties of myoglobin
  3. Structural and functional characterization of heme-DNA complexes
  4. Elucidation of structure-function relationship of cytochrome c
  5. Development of artificial blood-substitutes

3. Structural and functional characterization of heme-DNA complexes

Metalloporphyrins are quite frequently found as the prosthetic groups of a variety of hemoproteins exhibiting diverse biological functions. In such hemoproteins, the electronic nature of the metalloporphyrin is finely tuned through interaction with the surrounding protein moiety to allow a specific biological function. Despite the ubiquitous occurrence of various hemoproteins in nature, no functional role in vivo has yet been attributed to DNAs or RNAs possessing metalloporphyrins as prosthetic groups.

The G-quartet is formed from four guanine bases that are cyclically associated through Hoogsteen hydrogen-bonding. The size and planarity of the G-quartet are well-suited for interaction with heme through π-π stacking. Characterization of the molecular recognition between heme and the G-quartet is expected to provide knowledge for not only designing a stable complex between heme and a DNA, but also for tuning of the heme reactivity in the scaffold of the DNA structure. The solution structure of a single repeat sequence of the human telomere, d(TTAGGG), has been shown to form a parallel G-quadruplex DNA, i.e., (d(TTAGGG))4, in the presence of appropriate K+ concentrations. We found the formation of a stable complex between heme(Fe(III)) and (d(TTAGGG))4 (heme(Fe(III))-DNA complex). Interestingly, this heme-DNA complex exhibited various spectroscopic and functional properties remarkably similar to those of hemoproteins such as myoglobin. Thus, the heme(Fe(III))-DNA complex appeared to possess the structural essentials of the heme-deoxyribozymes that mimic hemoproteins in function.

Chemical structures of G-quartet and heme(left), steric structure(center) and scheatic drawing(right) of quadruplex DNA(d(TTAGGG)4)





1-1-1 Tennodai, Tsukuba Ibaraki 305-8571, Japan
Laboratory of Bioinorganic Chemistry,
Department of Chemistry,
Graduate School of Pure and Applied Sciences,Department of Chemistry, University of Tsukuba
Phone/Fax: +81-29-853-6521

2016.4.1 Update