2021 Fiscal Year Final Research Report
Elucidation of Molecular Mechanism for Activation of High-Valent Metal-Oxo species through their interaction with G-Quadruplexes and Creation of Novel DNAzymes
| Project/Area Number |
19H02824
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 37010:Bio-related chemistry
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
鈴木 秋弘 長岡工業高等専門学校, 物質工学科, 教授 (60179190)
百武 篤也 筑波大学, 数理物質系, 准教授 (70375369)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | 四重鎖DNA / Gカルテット / ヘム / 酸化触媒作用 / 機能性核酸 |
|---|
| Outline of Final Research Achievements |
Heme(Fe3+) binds to non-canonical G-quadruplex DNAs to form complexes (heme-DNAzymes) that exhibit peroxidase and peroxygenase activities. We found that the catalytic cycle of the heme-DNAzyme involves an iron(IV)oxo porphyrin π-cation radical intermediate known as Compound I formed through heterolytic O-O bond cleavage of an Fe-bound hydroperoxo ligand (Fe-OOH) in Compound 0. We also found that heme(Fe3+) binds selectively to the 3’-terminal G-quartet of the DNA, and a water molecule (AxH2O) sandwiched between the heme and G-quartet planes is coordinated to the heme Fe atom as an axial ligand. The polarization of AxH2O is thought to be considerably greater than that of an ordinary H2O molecule. Such unique electronic nature of AxH2O was found to be responsible for the catalytic activity of the heme-DNAzyme. We also found that the peroxidase activity of the heme-DNAzyme can be controlled through the local heme environment.
|
| Free Research Field |
生体関連化学
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究により、ヘムDNA酵素におけるヘムの機能の調節機構が解明された。ヘムDNA酵素の触媒サイクルでは、酵素ペルオキシダーゼとは異なる分子機構で、オキソ鉄４価ポルフィリンπカチオンラジカル錯体（Compound I）が反応中間体として生成することが明らかになった。ヘムDNA酵素のヘム鉄の軸配位子である水分子が、Compound Iの生成に重要な役割を担っていること、ヘムDNA酵素が示すヘムタンパク質類似の様々な分光学的性質をもたらしていることを発見した研究成果は、水分子の新しい機能および疎水性空間で孤立する水分子のユニークな物理化学的性質が解明されたという観点から、学術的な意義は大きい。
|
